Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicitie...Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.展开更多
The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis w...The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.展开更多
BACKGROUND Liver injury is a common complication of infection by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The utility of laboratory hematology data in the diagnosis and risk stratification ...BACKGROUND Liver injury is a common complication of infection by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The utility of laboratory hematology data in the diagnosis and risk stratification of patients with coronavirus disease 2019(COVID-19)has not been comprehensively examined.AIM To address the following.(1)Are the abnormalities in hematologic parameters seen in the general population of patients with COVID-19 also seen in those patients with associated liver injury?(2)Is liver injury in COVID-19 a sign of severe disease and does liver injury correlate with hematologic markers of severe disease?And(3)What is the quality of this evidence?METHODS To address these questions,a comprehensive systematic review was performed.We searched the peer reviewed medical literature using MEDLINE(PubMed interface),Web of Science,and EMBASE for cohort studies that specifically addressed liver injury and COVID-19 without limitation of date of publication or language.A quality assessment of the studies was performed using the Newcastle-Ottawa Scale.RESULTS Thirty-two articles were suitable for inclusion in our systematic review.These included 22 articles with a cohort of COVID-19 patients with liver injury,5 comparing non-severe vs severe COVID-19 populations in which liver injury was addressed,and 5 other cohort studies with a focus on liver injury.White blood cell count,absolute neutrophil count,absolute lymphocyte count(ALC),and hemoglobin were the parameters most helpful in distinguishing COVID-19 with liver injury from COVID-19 without liver injury.ALC and d-dimer were identified as being potentially useful in distinguishing non-severe from severe COVID-19. Liver injury was more frequently seen in cohorts with severe disease.Most studies were of high quality (24/48, 86%) with 4/28 (14%) of moderatequality and 0 of low quality.CONCLUSIONOur study supports the use of select hematologic parameters in diagnosis and riskstratification of liver injury in COVID-19 patients. Although of overall highquality, the current medical literature is limited by the small number of studieswith high statistical power and the variable definition of COVID-19 liver injury inthe literature.展开更多
BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnost...BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment.AIM To identify potentially valuable biomarkers for identifying CEA-negative CRC,the hematological characteristics of patients with CEA-negative CRC was investigated.METHODS In this retrospective analysis,74 patients were included who had been pathologically confirmed to have CEA-negative CRC,along with 79 individuals diagnosed with benign colorectal conditions.The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic(ROC)curve.RESULTS Compared with patients with benign colorectal diseases,those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio(HRR)and lymphocyte-to-red blood cell distribution width ratio(LRR),and higher platelet-to-lymphocyte ratio(PLR)(P<0.05).Correlation analysis showed that HRR was negatively correlated with T stage(r=-0.237),LRR was negatively correlated with T stage(r=-0.265)and distant metastasis(r=-0.321),and PLR was positively correlated with T stage(r=0.251)(all P<0.05).ROC analysis indicated that HRR outperformed LRR and PLR in identifying CEA-negative CRC.Combining HRR and PLR provided the highest area under the curve(area under the curve=0.808;sensitivity=82.43%;specificity=68.35%)for distinguishing CEA-negative CRC from benign colorectal diseases.CONCLUSION HRR,LRR,and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.展开更多
Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epige...Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events.Importantly,cyclin-dependent kinases(CDKs),complexed with their functional partner cyclins,play dominating roles in cell cycle control.Yet,efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes.Recently,mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase(WEE1)to modulate CDK activity,and correspondingly,a variety of therapeutic inhibitors have been developed to achieve clinical benefits.Thus,WEE1 may become a promising target to modulate the abnormal cell cycle.However,its function in hematologic diseases remains poorly elucidated.In this review,focusing on hematologic malignancies,we describe the biological structure of WEE1,emphasize the latest reported function of WEE1 in the carcinogenesis,progression,as well as prognosis,and finally summarize the therapeutic strategies by targeting WEE1.展开更多
Immuno-positron emission tomography(immuno-PET)is an innovative medical imaging technique that combines antibodies(Abs)or other immune-targeting molecules with positron-emitting radionuclides.By targeting antigens tha...Immuno-positron emission tomography(immuno-PET)is an innovative medical imaging technique that combines antibodies(Abs)or other immune-targeting molecules with positron-emitting radionuclides.By targeting antigens that are highly expressed in hematologic malignancies,immuno-PET has transformed diagnostic capabilities and enables precise monitoring of therapeutic responses through highly sensitive and specific tumor cell detection.Additionally,it plays a critical role in advancing therapeutic approaches by seamlessly linking diagnostic imaging with personalized treatment strategies.Its non-invasive nature and ability to provide whole-body imaging offer significant advantages over traditional diagnostic methods,especially for detecting minimal residual disease and guiding adaptive therapeutic interventions.In Ab-based immuno-PET,positronemitting radionuclides must have a half-life sufficient for slower pharmacokinetics and blood clearance of Abs.Recent studies have highlighted the advantages of long-lived radionuclides,such as 89Zr,which exhibit low positron energy and enable high sensitivity and resolution,making them particularly effective for tumor visualization and characterization.This review explores the current applications,recent advancements,and potential of immuno-PET for hematologic malignancies,emphasizing its pivotal role in improving patient outcomes and advancing precision medicine.展开更多
Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing G...Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing GIB,its safety and effectiveness in this high-risk group remain unclear.A recent study by Alhumayyd et al provided insight into this issue.However,it has notable limitations,including its retrospective nature,small sample size,and failure to adjust for important confounding factors such as disease severity,hemodynamic status,and platelet function.The study’s findings indicated that urgent endoscopy may help decrease the incidence of recurrent bleeding;however,it did not show a clear benefit in terms of mortality.Future research ought to prioritize prospective,multicenter studies that employ standardized protocols and incorporate risk stratification models to better understand the impact of endoscopic treatment for GIB in these patients.Additionally,integrating platelet function assays could improve clinical decision-making.Addressing these research gaps is essential for improving patient outcomes and developing effective guidelines for managing GIB in individuals with thrombocytopenia.展开更多
Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlyi...Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.展开更多
BACKGROUND Gastrointestinal bleeding(GIB)is a major cause of hospitalization worldwide.Patients with hematologic malignancies have a higher risk of GIB as a result of thrombocytopenia and platelet dysfunction.There is...BACKGROUND Gastrointestinal bleeding(GIB)is a major cause of hospitalization worldwide.Patients with hematologic malignancies have a higher risk of GIB as a result of thrombocytopenia and platelet dysfunction.There is no consensus on the optimal platelet level that would be safe for endoscopic intervention,although a platelet level of>50×10^(9)/L was suggested based on expert opinion.There is a paucity of data on whether endoscopic intervention and the timing of endoscopy impacted the outcome of patients with hematologic malignancy and severe thrombocytopenia who experienced acute overt GIB.AIM To assess the safety of endoscopic intervention of inpatients with hematological malignancies and severe thrombocytopenia presenting with acute overt GIB.METHODS This is a single center retrospective study.The data was collected from the electronic health record from 2018 to 2020.Inpatients with hematologic malignancy who presented with acute overt GIB and platelet count≤50×10^(9)/L were included in the study.Outcomes included mortality,transfusion requirements,length of stay,intensive care unit admission and recurrent bleeding.A subgroup analysis was performed to compare the outcomes of urgent endoscopy within 24 hours of GIB vs endoscopy>24 hours.RESULTS A total of 76 patients were identified.The mean platelet count is 24.3 in the endoscopy arm and 14.6 in the conservative management arm.There was no statistically significant difference between patients who had endoscopy vs conservative management in 30-day(P=0.13)or 1 year(P=0.78)mortality,recurrent bleeding(P=0.68),transfusion of red blood cells(P=0.47),platelets(P=0.31),or length of stay(P=0.94).A subgroup analysis comparing urgent endoscopy within 24 hours compared with delayed endoscopy showed urgent endoscopy was not associated with improved 30-day or 1 year mortality(P=0.11 and 0.46,respectively)compared to routine endoscopy,but was associated with decreased recurrent bleeding in 30 days(P=0.01).CONCLUSION Medical supportive treatment without endoscopy could be considered as an alternative to endoscopic therapy for patients with hematologic malignancy complicated by severe thrombocytopenia and acute non-variceal GIB.展开更多
Evidence on the association of occupational exposure to benzene,toluene,ethylbenzene,and xylene(BTEX)with hematologic and hepatic profiles were equivocal,and few studies have investigated overall effect of BTEX mixtur...Evidence on the association of occupational exposure to benzene,toluene,ethylbenzene,and xylene(BTEX)with hematologic and hepatic profiles were equivocal,and few studies have investigated overall effect of BTEX mixtures.Herein,significant higher concentrations(p<0.05)of hippuric acid,1,2-dihydroxybenzene,mandelic acid,trans,trans-muconic acid and phenylglyoxylic acid were found in petrochemical workers than the controls,in accordance with higher levels of hematologic and hepatic profiles found in petrochemical workers(p<0.05).Occupational exposure to individual BTEX was associated with elevated levels of white blood cell(WBC),lymphocyte(LYMPH),alanine aminotransferase(ALT),and gamma-glutamyl transferase(GGT).Further,the Weighted Quantile Sum Regression model and Bayesian Kernel Machine Regression model consistently identified a positive associa-tion between BTEX mixture exposure and WBC,LYMPH,and GGT.Xylene was the primary contributor to increased WBC,LYMPH,and GGT levels.Furthermore,BTEX exposure resulting in the increased inflammation indices were mainly related to perturbations of sphingolipid metabolism,biosynthesis of unsaturated fatty acids,and primary bile acid biosynthesis.Whereas metabolites mediated the correlation between BTEX exposure and liver function indiceswere related to the perturbations of biosynthesis of unsaturated fatty acids,arachidonic acid metabolism,sphingolipid metabolism,primary bile acid biosynthesis,etc.Our findings revealed potential health risk of occupational exposure to BTEX andmight help one to understand the link between BTEX exposure and hematologic and hepatic profiles.展开更多
Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and ...Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and timing of treatment.We intended to evaluate this using real-world data from patients of our regional hospital.This study also considers the role of immune status,including T-cell activation markers,in predicting vaccination success.Methods:Seventeen patients of our hospital having a hematological malignancy were included in this study,including myeloma,lymphoma,as well as acute myeloid leukemia(AML)and chronic lymphoid leukemia(CLL).All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)using Tozinameran following current recommendations.Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay.Immune status was determined from peripheral blood by flow cytometry.Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year.Patients were categorized as responders or non-responders,and differences in diagnosis,treatment,and immune status were analyzed.Results:Antibody response depended on both diagnosis and treatment.Active treatment directed against B-cells,such as anti-Cluster of Differentiation 20(CD20)therapy,was associated with weak seroconversion.For CD38-as well as proteasome-directed therapies,the data suggest that responders as well as non-responders exist.Notably,low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated withweak seroconversion upon vaccination.Conclusions:We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.展开更多
With the advances in allogeneic hematopoietic cell transplantation(allo-HCT)and supportive care,the number of allo-HCT for elderly patients has been increasing in recent years.However,the advanced donor age limits the...With the advances in allogeneic hematopoietic cell transplantation(allo-HCT)and supportive care,the number of allo-HCT for elderly patients has been increasing in recent years.However,the advanced donor age limits the availability of human leukocyte antigen(HLA)-matched sibling donors(MSD)for elderly individuals.展开更多
Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networ...Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networks(CNNs)excel in local feature extraction,their ability to capture global contextual relationships in complex cellular morphologies is limited.This study introduces a hybrid CNN-Transformer framework to enhance normal blood cell classification,laying the groundwork for future leukemia diagnostics.Methods:The proposed architecture integrates pre-trained CNNs(ResNet50,EfficientNetB3,InceptionV3,CustomCNN)with Vision Transformer(ViT)layers to combine local and global feature modeling.Four hybrid models were evaluated on the publicly available Blood Cell Images dataset from Kaggle,comprising 17,092 annotated normal blood cell images across eight classes.The models were trained using transfer learning,fine-tuning,and computational optimizations,including cross-model parameter sharing to reduce redundancy by reusing weights across CNN backbones and attention-guided layer pruning to eliminate low-contribution layers based on attention scores,improving efficiency without sacrificing accuracy.Results:The InceptionV3-ViT model achieved a weighted accuracy of 97.66%(accounting for class imbalance by weighting each class’s contribution),a macro F1-score of 0.98,and a ROC-AUC of 0.998.The framework excelled in distinguishing morphologically similar cell types demonstrating robustness and reliable calibration(ECE of 0.019).The framework addresses generalization challenges,including class imbalance and morphological similarities,ensuring robust performance across diverse cell types.Conclusion:The hybrid CNN-Transformer framework significantly improves normal blood cell classification by capturing multi-scale features and long-range dependencies.Its high accuracy,efficiency,and generalization position it as a strong baseline for automated hematological analysis,with potential for extension to leukemia subtype classification through future validation on pathological samples.展开更多
Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs ...Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).展开更多
Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those inv...Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those involving hemolysis or impaired erythropoiesis,may play a significant role in the formation of gallblad-der stones,predominantly pigment stones.This review explores the pathophysio-logical mechanisms linking hematological disorders,such as hemolytic anemias,myeloproliferative disorders,and hematological malignancies,with gallbladder stone development.We also examine the influence of treatments for hemato-logical conditions,such as blood transfusions and chemotherapy,on gallstone risk.Additionally,this article discusses the clinical implications of gallbladder stones in patients with hematological disorders,including diagnostic challenges,management strategies,and surgical considerations.By providing a compre-hensive overview of current knowledge,this review aims to highlight the need for further research into the interplay between hematological disorders and gall-bladder stones,potentially improving preventive and therapeutic strategies in these patient populations.展开更多
Atrial fibrillation(AF)is a frequent cardiac arrhythmia in the general population,which is associated with an increased risk of several health issues.It has been demonstrated that hematological variables predict the o...Atrial fibrillation(AF)is a frequent cardiac arrhythmia in the general population,which is associated with an increased risk of several health issues.It has been demonstrated that hematological variables predict the occurrence and recurrence of AF.This review article specifically only focuses on haemoglobin,hematocrit,platelet count,white blood cells(WBCs),lymphocytes,neutrophils,monocytes,neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR)and red blood cells in the pathophysiology of AF.It emphasizes that there is a higher risk of new-onset AF linked with both low and high haemoglobin levels.A quantitative investigation showed that hematocrit is not linked to the development of AF.The predictive significance of platelet count was reported in nonvalvular AF patients.WBCs are consistent inflammatory markers that are associated with postoperative new-onset AF.Inflammation and in particular,leukocyte activation predisposes to AF.Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.In particular,the peripheral eosinophil and left atrial diameter may be important in mediating inflammation and atrial remodeling in AF.In nonvalvular AF patients,PLR may be an independent risk factor for left atrial appendage thrombogenic milieu.NLR and MLR changes are associated with early recurrence of AF,and NLR change is related to late recurrence of AF after pulmonary vein isolation.Red blood cell distribution width and left atrial dimension were the only independent risk factors associated with AF.展开更多
BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We ...BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.展开更多
BACKGROUND Gastric cancer is a major global health concern,often diagnosed at advanced stages,leading to poor prognosis.Proximal and distal gastric cancers exhibit distinct clinicopathological features.AIM To investig...BACKGROUND Gastric cancer is a major global health concern,often diagnosed at advanced stages,leading to poor prognosis.Proximal and distal gastric cancers exhibit distinct clinicopathological features.AIM To investigate the diagnostic value of hematological and inflammatory markers in differentiating proximal and distal gastric cancers and to evaluate their association with clinical outcomes.METHODS A retrospective cohort study was conducted on 150 patients diagnosed with gastric adenocarcinoma through histopathological analysis.Patients were categorized into proximal gastric cancer and distal gastric cancer groups.Laboratory parameters were analyzed.RESULTS Of the 150 patients,84 had proximal gastric cancer and 66 had distal gastric cancer.Dysphagia was significantly more common in the proximal gastric cancer group,while anemia and higher platelet-to-lymphocyte ratio values were observed in the distal gastric cancer group(P=0.031).Tumor stage and neutrophil-to-lymphocyte ratio emerged as independent predictors of all-cause mortality.No significant differences were found in other laboratory or biochemical parameters between the groups.CONCLUSION Proximal and distal gastric cancers demonstrate distinct clinical and laboratory profiles.The platelet-to-lymphocyte ratio may serve as a valuable marker in differentiating cancer localization,while the neutrophil-to-lymphocyte ratio is a prognostic indicator for mortality.These findings highlight the potential of hematological markers in optimizing diagnosis and treatment strategies for gastric cancer.展开更多
Objectives:Immunomodulatory drugs(IMiDs),functioning as molecular glue degraders,have been approved for treating various hematological malignancies;however,the inevitable acquired drug resistance resulting from their ...Objectives:Immunomodulatory drugs(IMiDs),functioning as molecular glue degraders,have been approved for treating various hematological malignancies;however,the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment.The study aimed to develop degraders with potent efficiency and low toxicity.Methods:Phenotypic profiling,elaborate structure-activity relationships(SAR),rational drug design and degradation profiles investigations,quantitative proteomics analysis and cell-based functional studies,and pharmacokinetic studies were conducted to develop more potent degraders.Results:This study developed novel CRBN-binding moieties throughmethylene deletion in lenalidomide’s isoindole core.Lead compounds MGD-A7 and MGD-C9 demonstrated superior antiproliferative efficacy vs.IMiDs,with submicromolar potency.MGD-A7 and MGD-C9 significantly and selectively induced the degradation of Ikaros Family Zinc Finger Proteins 1 and 3(IKZF1/3)with nanomolar potency via a CRBN-dependent pathway.Mechanistically,MGD-A7 and MGD-C9 dramatically induced cell apoptosis and G1 cell cycle arrest and MGDC9 exhibited favorable pharmacokinetic properties in vivo.Furthermore,MGD-C9 exhibited significant synergistic effects with standard-of-care agents in various hematological malignancy cells.Conclusions:These results indicate that MGD-C9 could act as a highly effective CRBN ligand and is expected to become a candidate drug for the treatment of hematological malignancies.展开更多
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
基金the National Natural Science Foundation of China(No.81230014,No.81470341,No.81520108002 and No.81500157)the Key Project of Science and Technology Department of Zhejiang Province(No.2018C03016-2)the Key Research and Development Program of Zhejiang Province(No.2019C03016).
文摘Chimeric antigen receptor T(CAR-T)cell therapy is the novel treatment strategy for hematological malignancies such as acute lymphoblastic leukemia(ALL),lymphoma and multiple myeloma.However,treatment-related toxicities such as cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)have become significant hurdles to CAR-T treatment.Multiple strategies were established to alter the CAR structure on the genomic level to improve efficacy and reduce toxicities.Recently,the innovative gene-editing technology-clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease9(Cas9)system,which particularly exhibits preponderance in knock-in and knockout at specific sites,is widely utilized to manufacture CAR-T products.The application of CRISPR/Cas9 to CAR-T cell therapy has shown promising clinical results with minimal toxicity.In this review,we summarized the past achievements of CRISPR/Cas9 in CAR-T therapy and focused on the potential CAR-T targets.
文摘The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.
文摘BACKGROUND Liver injury is a common complication of infection by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The utility of laboratory hematology data in the diagnosis and risk stratification of patients with coronavirus disease 2019(COVID-19)has not been comprehensively examined.AIM To address the following.(1)Are the abnormalities in hematologic parameters seen in the general population of patients with COVID-19 also seen in those patients with associated liver injury?(2)Is liver injury in COVID-19 a sign of severe disease and does liver injury correlate with hematologic markers of severe disease?And(3)What is the quality of this evidence?METHODS To address these questions,a comprehensive systematic review was performed.We searched the peer reviewed medical literature using MEDLINE(PubMed interface),Web of Science,and EMBASE for cohort studies that specifically addressed liver injury and COVID-19 without limitation of date of publication or language.A quality assessment of the studies was performed using the Newcastle-Ottawa Scale.RESULTS Thirty-two articles were suitable for inclusion in our systematic review.These included 22 articles with a cohort of COVID-19 patients with liver injury,5 comparing non-severe vs severe COVID-19 populations in which liver injury was addressed,and 5 other cohort studies with a focus on liver injury.White blood cell count,absolute neutrophil count,absolute lymphocyte count(ALC),and hemoglobin were the parameters most helpful in distinguishing COVID-19 with liver injury from COVID-19 without liver injury.ALC and d-dimer were identified as being potentially useful in distinguishing non-severe from severe COVID-19. Liver injury was more frequently seen in cohorts with severe disease.Most studies were of high quality (24/48, 86%) with 4/28 (14%) of moderatequality and 0 of low quality.CONCLUSIONOur study supports the use of select hematologic parameters in diagnosis and riskstratification of liver injury in COVID-19 patients. Although of overall highquality, the current medical literature is limited by the small number of studieswith high statistical power and the variable definition of COVID-19 liver injury inthe literature.
基金Supported by Youth Project of Guangxi International Zhuang Medicine Hospital,No.[2022]203Discipline Project of Guangxi International Zhuang Medicine Hospital,No.[2021]33Research Fund of Guangxi International Zhuang Medicine Hospital,No.RCYJ202201.
文摘BACKGROUND Colorectal cancer(CRC)remains one of the most common malignancies worldwide,with a significant subset of patients exhibiting absence of carcinoembryonic-antigen(CEA)expression.The lack of effective diagnostic method for CEA-negative CRC prevents its early treatment.AIM To identify potentially valuable biomarkers for identifying CEA-negative CRC,the hematological characteristics of patients with CEA-negative CRC was investigated.METHODS In this retrospective analysis,74 patients were included who had been pathologically confirmed to have CEA-negative CRC,along with 79 individuals diagnosed with benign colorectal conditions.The utility of various biomarkers was evaluated using analysis of the receiver operating characteristic(ROC)curve.RESULTS Compared with patients with benign colorectal diseases,those with CEA-negative CRC had lower hemoglobin-to-red blood cell distribution width ratio(HRR)and lymphocyte-to-red blood cell distribution width ratio(LRR),and higher platelet-to-lymphocyte ratio(PLR)(P<0.05).Correlation analysis showed that HRR was negatively correlated with T stage(r=-0.237),LRR was negatively correlated with T stage(r=-0.265)and distant metastasis(r=-0.321),and PLR was positively correlated with T stage(r=0.251)(all P<0.05).ROC analysis indicated that HRR outperformed LRR and PLR in identifying CEA-negative CRC.Combining HRR and PLR provided the highest area under the curve(area under the curve=0.808;sensitivity=82.43%;specificity=68.35%)for distinguishing CEA-negative CRC from benign colorectal diseases.CONCLUSION HRR,LRR,and PLR alone or in combination could be used to distinguish CEA-negative CRC from benign colorectal diseases.
基金supported by grants from the National Natural Science Foundation of China(No.81920108004,82270127,82203880)the Hunan Provincial Natural Science Foundation of China(No.2023JJ30928,2024JJ3037)+2 种基金the Changsha Municipal Natural Sci-Science Foundation(No.kq2208382)the Fellowship of the China Postdoctoral Science Foundation(No.2023T160740)the Hunan Province Clinical Medical Technology Innovation Guidance Project(No.2021SK50917,2023SK4056)。
文摘Hematologic malignancies,including leukemia,lymphoma,and multiple myeloma,are hazardous diseases characterized by the uncontrolled proliferation of cancer cells.Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events.Importantly,cyclin-dependent kinases(CDKs),complexed with their functional partner cyclins,play dominating roles in cell cycle control.Yet,efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes.Recently,mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase(WEE1)to modulate CDK activity,and correspondingly,a variety of therapeutic inhibitors have been developed to achieve clinical benefits.Thus,WEE1 may become a promising target to modulate the abnormal cell cycle.However,its function in hematologic diseases remains poorly elucidated.In this review,focusing on hematologic malignancies,we describe the biological structure of WEE1,emphasize the latest reported function of WEE1 in the carcinogenesis,progression,as well as prognosis,and finally summarize the therapeutic strategies by targeting WEE1.
文摘Immuno-positron emission tomography(immuno-PET)is an innovative medical imaging technique that combines antibodies(Abs)or other immune-targeting molecules with positron-emitting radionuclides.By targeting antigens that are highly expressed in hematologic malignancies,immuno-PET has transformed diagnostic capabilities and enables precise monitoring of therapeutic responses through highly sensitive and specific tumor cell detection.Additionally,it plays a critical role in advancing therapeutic approaches by seamlessly linking diagnostic imaging with personalized treatment strategies.Its non-invasive nature and ability to provide whole-body imaging offer significant advantages over traditional diagnostic methods,especially for detecting minimal residual disease and guiding adaptive therapeutic interventions.In Ab-based immuno-PET,positronemitting radionuclides must have a half-life sufficient for slower pharmacokinetics and blood clearance of Abs.Recent studies have highlighted the advantages of long-lived radionuclides,such as 89Zr,which exhibit low positron energy and enable high sensitivity and resolution,making them particularly effective for tumor visualization and characterization.This review explores the current applications,recent advancements,and potential of immuno-PET for hematologic malignancies,emphasizing its pivotal role in improving patient outcomes and advancing precision medicine.
文摘Gastrointestinal bleeding(GIB)presents a significant challenge for patients with hematologic malignancies,especially those with severe thrombocytopenia.Although endoscopic intervention is frequently used in managing GIB,its safety and effectiveness in this high-risk group remain unclear.A recent study by Alhumayyd et al provided insight into this issue.However,it has notable limitations,including its retrospective nature,small sample size,and failure to adjust for important confounding factors such as disease severity,hemodynamic status,and platelet function.The study’s findings indicated that urgent endoscopy may help decrease the incidence of recurrent bleeding;however,it did not show a clear benefit in terms of mortality.Future research ought to prioritize prospective,multicenter studies that employ standardized protocols and incorporate risk stratification models to better understand the impact of endoscopic treatment for GIB in these patients.Additionally,integrating platelet function assays could improve clinical decision-making.Addressing these research gaps is essential for improving patient outcomes and developing effective guidelines for managing GIB in individuals with thrombocytopenia.
文摘Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.
文摘BACKGROUND Gastrointestinal bleeding(GIB)is a major cause of hospitalization worldwide.Patients with hematologic malignancies have a higher risk of GIB as a result of thrombocytopenia and platelet dysfunction.There is no consensus on the optimal platelet level that would be safe for endoscopic intervention,although a platelet level of>50×10^(9)/L was suggested based on expert opinion.There is a paucity of data on whether endoscopic intervention and the timing of endoscopy impacted the outcome of patients with hematologic malignancy and severe thrombocytopenia who experienced acute overt GIB.AIM To assess the safety of endoscopic intervention of inpatients with hematological malignancies and severe thrombocytopenia presenting with acute overt GIB.METHODS This is a single center retrospective study.The data was collected from the electronic health record from 2018 to 2020.Inpatients with hematologic malignancy who presented with acute overt GIB and platelet count≤50×10^(9)/L were included in the study.Outcomes included mortality,transfusion requirements,length of stay,intensive care unit admission and recurrent bleeding.A subgroup analysis was performed to compare the outcomes of urgent endoscopy within 24 hours of GIB vs endoscopy>24 hours.RESULTS A total of 76 patients were identified.The mean platelet count is 24.3 in the endoscopy arm and 14.6 in the conservative management arm.There was no statistically significant difference between patients who had endoscopy vs conservative management in 30-day(P=0.13)or 1 year(P=0.78)mortality,recurrent bleeding(P=0.68),transfusion of red blood cells(P=0.47),platelets(P=0.31),or length of stay(P=0.94).A subgroup analysis comparing urgent endoscopy within 24 hours compared with delayed endoscopy showed urgent endoscopy was not associated with improved 30-day or 1 year mortality(P=0.11 and 0.46,respectively)compared to routine endoscopy,but was associated with decreased recurrent bleeding in 30 days(P=0.01).CONCLUSION Medical supportive treatment without endoscopy could be considered as an alternative to endoscopic therapy for patients with hematologic malignancy complicated by severe thrombocytopenia and acute non-variceal GIB.
基金supported by the National Key Research and Development Project(Nos.2019YFC1804503 and 2019YFC1804502)the National Natural Science Foundation of China(Nos.42307477 and 42207485)Guangdong Provincial Key R&D Program(No.2022-GDUT-A0007).
文摘Evidence on the association of occupational exposure to benzene,toluene,ethylbenzene,and xylene(BTEX)with hematologic and hepatic profiles were equivocal,and few studies have investigated overall effect of BTEX mixtures.Herein,significant higher concentrations(p<0.05)of hippuric acid,1,2-dihydroxybenzene,mandelic acid,trans,trans-muconic acid and phenylglyoxylic acid were found in petrochemical workers than the controls,in accordance with higher levels of hematologic and hepatic profiles found in petrochemical workers(p<0.05).Occupational exposure to individual BTEX was associated with elevated levels of white blood cell(WBC),lymphocyte(LYMPH),alanine aminotransferase(ALT),and gamma-glutamyl transferase(GGT).Further,the Weighted Quantile Sum Regression model and Bayesian Kernel Machine Regression model consistently identified a positive associa-tion between BTEX mixture exposure and WBC,LYMPH,and GGT.Xylene was the primary contributor to increased WBC,LYMPH,and GGT levels.Furthermore,BTEX exposure resulting in the increased inflammation indices were mainly related to perturbations of sphingolipid metabolism,biosynthesis of unsaturated fatty acids,and primary bile acid biosynthesis.Whereas metabolites mediated the correlation between BTEX exposure and liver function indiceswere related to the perturbations of biosynthesis of unsaturated fatty acids,arachidonic acid metabolism,sphingolipid metabolism,primary bile acid biosynthesis,etc.Our findings revealed potential health risk of occupational exposure to BTEX andmight help one to understand the link between BTEX exposure and hematologic and hepatic profiles.
基金supported by a grant of the Deutsche Forschungsgemeinschaft(DFG)to G.B.(#405833349).
文摘Background:Patients with hemato-oncological malignancies may respond insufficiently to vaccination,especially in terms of antibody titer.The antibody response depends on the type of malignancy as well as the type and timing of treatment.We intended to evaluate this using real-world data from patients of our regional hospital.This study also considers the role of immune status,including T-cell activation markers,in predicting vaccination success.Methods:Seventeen patients of our hospital having a hematological malignancy were included in this study,including myeloma,lymphoma,as well as acute myeloid leukemia(AML)and chronic lymphoid leukemia(CLL).All patients were vaccinated against Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)using Tozinameran following current recommendations.Circulating antibodies directed against the spike protein of SARS-CoV-2 were determined by a commercial immune assay.Immune status was determined from peripheral blood by flow cytometry.Both parameters were followed in fifteen patients who provided sufficient follow-up data for up to one year.Patients were categorized as responders or non-responders,and differences in diagnosis,treatment,and immune status were analyzed.Results:Antibody response depended on both diagnosis and treatment.Active treatment directed against B-cells,such as anti-Cluster of Differentiation 20(CD20)therapy,was associated with weak seroconversion.For CD38-as well as proteasome-directed therapies,the data suggest that responders as well as non-responders exist.Notably,low peripheral B-cell numbers and high CD3+HLADR+cell counts correlated withweak seroconversion upon vaccination.Conclusions:We suggest that peripheral immune status can be applied as a predictive biomarker for seroconversion upon vaccinations.
基金supported by National Natural Science Foundation of China(No.82370215,82020108003,and 82330008)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Jiangsu Provincial Medical Innovation Center(No.CXZX202201)Science and Technology Program of Suzhou(No.SKY2023047)。
文摘With the advances in allogeneic hematopoietic cell transplantation(allo-HCT)and supportive care,the number of allo-HCT for elderly patients has been increasing in recent years.However,the advanced donor age limits the availability of human leukocyte antigen(HLA)-matched sibling donors(MSD)for elderly individuals.
基金the Deanship of Graduate Studies and Scientific Research at Najran University,Saudi Arabia,for their financial support through the Easy Track Research program,grant code(NU/EFP/MRC/13).
文摘Background:Accurate classification of normal blood cells is a critical foundation for automated hematological analysis,including the detection of pathological conditions like leukemia.While convolutional neural networks(CNNs)excel in local feature extraction,their ability to capture global contextual relationships in complex cellular morphologies is limited.This study introduces a hybrid CNN-Transformer framework to enhance normal blood cell classification,laying the groundwork for future leukemia diagnostics.Methods:The proposed architecture integrates pre-trained CNNs(ResNet50,EfficientNetB3,InceptionV3,CustomCNN)with Vision Transformer(ViT)layers to combine local and global feature modeling.Four hybrid models were evaluated on the publicly available Blood Cell Images dataset from Kaggle,comprising 17,092 annotated normal blood cell images across eight classes.The models were trained using transfer learning,fine-tuning,and computational optimizations,including cross-model parameter sharing to reduce redundancy by reusing weights across CNN backbones and attention-guided layer pruning to eliminate low-contribution layers based on attention scores,improving efficiency without sacrificing accuracy.Results:The InceptionV3-ViT model achieved a weighted accuracy of 97.66%(accounting for class imbalance by weighting each class’s contribution),a macro F1-score of 0.98,and a ROC-AUC of 0.998.The framework excelled in distinguishing morphologically similar cell types demonstrating robustness and reliable calibration(ECE of 0.019).The framework addresses generalization challenges,including class imbalance and morphological similarities,ensuring robust performance across diverse cell types.Conclusion:The hybrid CNN-Transformer framework significantly improves normal blood cell classification by capturing multi-scale features and long-range dependencies.Its high accuracy,efficiency,and generalization position it as a strong baseline for automated hematological analysis,with potential for extension to leukemia subtype classification through future validation on pathological samples.
文摘Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).
文摘Gallbladder stones,a prevalent biliary tract disease,have multifactorial etiologies including metabolic,genetic,and environmental factors.Emerging evidence su-ggests that hematological disorders,particularly those involving hemolysis or impaired erythropoiesis,may play a significant role in the formation of gallblad-der stones,predominantly pigment stones.This review explores the pathophysio-logical mechanisms linking hematological disorders,such as hemolytic anemias,myeloproliferative disorders,and hematological malignancies,with gallbladder stone development.We also examine the influence of treatments for hemato-logical conditions,such as blood transfusions and chemotherapy,on gallstone risk.Additionally,this article discusses the clinical implications of gallbladder stones in patients with hematological disorders,including diagnostic challenges,management strategies,and surgical considerations.By providing a compre-hensive overview of current knowledge,this review aims to highlight the need for further research into the interplay between hematological disorders and gall-bladder stones,potentially improving preventive and therapeutic strategies in these patient populations.
文摘Atrial fibrillation(AF)is a frequent cardiac arrhythmia in the general population,which is associated with an increased risk of several health issues.It has been demonstrated that hematological variables predict the occurrence and recurrence of AF.This review article specifically only focuses on haemoglobin,hematocrit,platelet count,white blood cells(WBCs),lymphocytes,neutrophils,monocytes,neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),platelet-to-lymphocyte ratio(PLR)and red blood cells in the pathophysiology of AF.It emphasizes that there is a higher risk of new-onset AF linked with both low and high haemoglobin levels.A quantitative investigation showed that hematocrit is not linked to the development of AF.The predictive significance of platelet count was reported in nonvalvular AF patients.WBCs are consistent inflammatory markers that are associated with postoperative new-onset AF.Inflammation and in particular,leukocyte activation predisposes to AF.Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.In particular,the peripheral eosinophil and left atrial diameter may be important in mediating inflammation and atrial remodeling in AF.In nonvalvular AF patients,PLR may be an independent risk factor for left atrial appendage thrombogenic milieu.NLR and MLR changes are associated with early recurrence of AF,and NLR change is related to late recurrence of AF after pulmonary vein isolation.Red blood cell distribution width and left atrial dimension were the only independent risk factors associated with AF.
文摘BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.
基金This study was approved by the Agrı Training and Research Hospital Scientific Research Ethics Committee(No.E-95531838-050.99-86900)conducted in accordance with the Declaration of Helsinki.
文摘BACKGROUND Gastric cancer is a major global health concern,often diagnosed at advanced stages,leading to poor prognosis.Proximal and distal gastric cancers exhibit distinct clinicopathological features.AIM To investigate the diagnostic value of hematological and inflammatory markers in differentiating proximal and distal gastric cancers and to evaluate their association with clinical outcomes.METHODS A retrospective cohort study was conducted on 150 patients diagnosed with gastric adenocarcinoma through histopathological analysis.Patients were categorized into proximal gastric cancer and distal gastric cancer groups.Laboratory parameters were analyzed.RESULTS Of the 150 patients,84 had proximal gastric cancer and 66 had distal gastric cancer.Dysphagia was significantly more common in the proximal gastric cancer group,while anemia and higher platelet-to-lymphocyte ratio values were observed in the distal gastric cancer group(P=0.031).Tumor stage and neutrophil-to-lymphocyte ratio emerged as independent predictors of all-cause mortality.No significant differences were found in other laboratory or biochemical parameters between the groups.CONCLUSION Proximal and distal gastric cancers demonstrate distinct clinical and laboratory profiles.The platelet-to-lymphocyte ratio may serve as a valuable marker in differentiating cancer localization,while the neutrophil-to-lymphocyte ratio is a prognostic indicator for mortality.These findings highlight the potential of hematological markers in optimizing diagnosis and treatment strategies for gastric cancer.
基金supported by the National Natural Science Foundation of China(No.82404417)Key Project of North China University of Science and Technology(ZD-YG-202408)State Key Laboratory of National Security Specially Needed Medicines Program(No.LTMC2022ZZ006).
文摘Objectives:Immunomodulatory drugs(IMiDs),functioning as molecular glue degraders,have been approved for treating various hematological malignancies;however,the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment.The study aimed to develop degraders with potent efficiency and low toxicity.Methods:Phenotypic profiling,elaborate structure-activity relationships(SAR),rational drug design and degradation profiles investigations,quantitative proteomics analysis and cell-based functional studies,and pharmacokinetic studies were conducted to develop more potent degraders.Results:This study developed novel CRBN-binding moieties throughmethylene deletion in lenalidomide’s isoindole core.Lead compounds MGD-A7 and MGD-C9 demonstrated superior antiproliferative efficacy vs.IMiDs,with submicromolar potency.MGD-A7 and MGD-C9 significantly and selectively induced the degradation of Ikaros Family Zinc Finger Proteins 1 and 3(IKZF1/3)with nanomolar potency via a CRBN-dependent pathway.Mechanistically,MGD-A7 and MGD-C9 dramatically induced cell apoptosis and G1 cell cycle arrest and MGDC9 exhibited favorable pharmacokinetic properties in vivo.Furthermore,MGD-C9 exhibited significant synergistic effects with standard-of-care agents in various hematological malignancy cells.Conclusions:These results indicate that MGD-C9 could act as a highly effective CRBN ligand and is expected to become a candidate drug for the treatment of hematological malignancies.
