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
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
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
Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of t...Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers,but also enables the detection of solid tumors.Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities,such as in fine-needle biopsy samples.This attribute not only addresses the challenge posed by small sample sizes,but also boosts the sensitivity of tumor cell detection.The significance of FCM in clinical and pathological applications continues to grow.To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process,experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus.This consensus was formulated based on current literature and clinical practices of all experts across clinical,laboratory,and pathological fields in China.It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples,including report content,interpretation,quality control,and key considerations.Additionally,it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests,particularly in cases with limited sample sizes.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
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 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
Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(...Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.展开更多
BACKGROUND Visceral leishmaniasis(VL)is a systemic protozoan infection caused by Leishmania donovani(L.donovani)and transmitted by sand flies,causing macrophage invasion in the liver,spleen,and bone marrow.Diagnosis o...BACKGROUND Visceral leishmaniasis(VL)is a systemic protozoan infection caused by Leishmania donovani(L.donovani)and transmitted by sand flies,causing macrophage invasion in the liver,spleen,and bone marrow.Diagnosis of VL is currently based on clinical signs,symptoms,and specific in-vitro markers and bone marrow investigations.However,VL's specific hematological and bone marrow manifestation in Sudanese pediatric patients is not well studied.AIM To examine the blood and bone marrow characteristics in pediatric patients from Sudan who have VL.METHODS This is a retrospective hospital-based study with a sample of 107 consecutive Sudanese pediatric patients.The data focused on hematological and bone marrow results.We included only the completed records of the pediatric patients with VL in the Tropical Disease Teaching Hospital in Khartoum,Sudan from the period of 2016 to 2020.RESULTS The majority of pediatric patients included in this study are below 5-years-old(n=59,55.2%).Moreover,anemia,thrombocytopenia,and leukopenia were among the prevalent characteristics in the population under study.To further analyze the data,we developed a machine learning model using boosted forest algorithms to predict L.donovani parasites load,with a mean accuracy of 0.88 for the training dataset and an accuracy of 0.46,0.50,and 0.74 for mild,moderate,and severe L.donovani parasite load in the validation dataset.CONCLUSION This study shows that the most common bone marrow change among Sudanese VL children was increased chronic inflammatory cells(n=88,82.2%)with present macrophage hemophagocytes(n=103,96.3%).While anemia and thrombocytopenia were the most common hematological changes.These results will hopefully lead to an early diagnosis and hence better management for Sudanese pediatric patients with suspected VL.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:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the mo...Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.展开更多
In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HB...In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.展开更多
Patients with hematological tumors experience physical and psychological stress,and negative psychological states.Baduanjin,an emerging psychological rehabil-itation method combined with resistance exercise,has receiv...Patients with hematological tumors experience physical and psychological stress,and negative psychological states.Baduanjin,an emerging psychological rehabil-itation method combined with resistance exercise,has received widespread attention.This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects.Through a literature review and comprehensive analysis,the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated.The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors,which can alleviate anxiety,depression,and other adverse emotions,and improve quality of life.However,there is a lack of unified and standardized exercise intervention programs for practical application,and patient participation and compliance must be improved.Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors;however,it is still necessary to further standardize and improve the exercise program improving patient participation and compliance.Future studies should strengthen theoretical exploration and empirical research,providing more effective psychological rehabilitation strategies for patients with hematological tumors.展开更多
Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to ad...Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.展开更多
Research Background: Malaria, predominantly caused by Plasmodium falciparum, continues to be a leading cause of morbidity and mortality among children under five years of age in sub-Saharan Africa. Malaria remains a s...Research Background: Malaria, predominantly caused by Plasmodium falciparum, continues to be a leading cause of morbidity and mortality among children under five years of age in sub-Saharan Africa. Malaria remains a significant public health challenge in Nigeria, particularly in regions where access to healthcare facilities is limited. Home-based management of malaria has emerged as a critical strategy to reduce disease burden, enabling timely treatment at the community level. Chloroquine, once the cornerstone of malaria treatment, is still utilized in some settings due to its affordability, availability, oral administration, and historical effectiveness against Plasmodium species. However, the widespread emergence of chloroquine-resistant strains of Plasmodium falciparum has necessitated a reevaluation of its role in malaria management. This study investigates the therapeutic effectiveness of oral chloroquine in home-based management, focusing on its ability to reduce parasitemia and alleviate clinical symptoms. Additionally, the study assessed the influence of protein nutritional status and bacterial/viral co-infections on malaria outcomes among children under five years in Jos, Nigeria, providing insights into its current relevance in resource-limited settings. Research Objective: Given the historical use of chloroquine and emerging reports of chloroquine-sensitive strains, this research aims to evaluate the therapeutic effectiveness of oral chloroquine in the home-based management of childhood malaria in Jos, Nigeria, by assessing its impact on parasitemia, symptom alleviation, biochemical and hematological profiles, nutritional status, and interactions with co-infections while providing evidence-based insights to inform policy, community health practices, and contemporary malaria control strategies. Methods: This cross-sectional and analytical study evaluated the role of oral chloroquine in the home-based management of childhood malaria in Jos, Nigeria. A total of 93 children under five years of age, presenting with fever and confirmed Plasmodium falciparum parasitemia, were recruited from two hospitals in Jos. Participants were stratified into three groups: children treated with chloroquine at home prior to hospital presentation, untreated children with uncomplicated malaria, and untreated children with severe malaria. Caregivers were surveyed to assess the use of chloroquine as a first-line home treatment, including dosage and timing of administration. Ethical approval was obtained from the Jos University Teaching Hospital (JUTH) Ethical Committee, and informed consent was secured from caregivers before sample collection and interviews. Parasitemia levels were measured to correlate parasite density with clinical outcomes. Comprehensive assessments included biochemical analysis of serum creatinine, liver enzymes, and protein levels to evaluate organ function and metabolic status. Hematological parameters, including hemoglobin concentration and red blood cell (RBC) count, were measured to assess malaria severity and anemia. Nutritional status was evaluated through anthropometric measurements and serum protein analyses. Co-infections with bacterial and viral pathogens were identified using microscopic examination of blood samples. Statistical analyses were performed to identify significant associations between chloroquine treatment, clinical outcomes, and biochemical indicators. Results: Children treated with chloroquine demonstrated significantly lower parasitemia levels (18.13%) compared to untreated children with uncomplicated malaria (34.35%) and those with severe malaria (43.57%). Hemoglobin levels were notably higher in the chloroquine-treated group (9.60 g/dL) compared to the untreated groups, indicating a reduced burden of malaria-induced anemia. Body temperatures were significantly lower among chloroquine-treated children, underscoring its efficacy in fever reduction. Bacterial co-infections were identified in 54.35% of malaria cases, emphasizing their role in exacerbating disease severity. Liver and kidney function tests revealed no significant differences between the groups, indicating that chloroquine treatment did not result in hepatic or renal toxicity. Additionally, all participants exhibited adequate nutritional status, with no evidence of protein-energy malnutrition. Conclusion: The findings of this study highlight the significant role of oral chloroquine in the home-based management of childhood malaria in Jos, Nigeria. Children treated with chloroquine exhibited substantially lower parasitemia levels and higher hemoglobin concentrations compared to untreated children, demonstrating its effectiveness in reducing parasite burden and mitigating malaria-induced anemia. Additionally, chloroquine treatment was associated with lower body temperatures, reflecting its efficacy in fever control. Bacterial co-infections were present in over half of the malaria cases (54.35%), underscoring their potential contribution to disease severity and the need for integrated management strategies. Importantly, liver and kidney function tests showed no significant differences among the groups, indicating that chloroquine use did not lead to hepatic or renal toxicity. Furthermore, all participants maintained adequate nutritional status, with no signs of protein-energy malnutrition. These results support the continued use of chloroquine as a viable option in the home-based management of uncomplicated malaria while highlighting the importance of addressing co-infections to improve clinical outcomes.展开更多
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.
基金supported by grants from the National Natural Science Foundation of China(grant numbers:82370195,82270203,81770211)the Fundamental Research Funds for the Central Univer-sities(grant number:2022CDJYGRH-001)Chongqing Technology Innovation and Application Development Special Key Project(grant number:CSTB2024TIAD-KPX0031).
文摘Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers,but also enables the detection of solid tumors.Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities,such as in fine-needle biopsy samples.This attribute not only addresses the challenge posed by small sample sizes,but also boosts the sensitivity of tumor cell detection.The significance of FCM in clinical and pathological applications continues to grow.To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process,experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus.This consensus was formulated based on current literature and clinical practices of all experts across clinical,laboratory,and pathological fields in China.It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples,including report content,interpretation,quality control,and key considerations.Additionally,it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests,particularly in cases with limited sample sizes.
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.
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.
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.
基金supported by the National Key R&D Program of China (2019YFA0508502/3 and 2021YFC2300604)the Natural Science Foundation of China (Reference numbers 82388201, 82241216, and 32270963)+1 种基金the Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220008)the Anhui Key Research and Development Plan (Reference number 2023z04020011)。
文摘Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.
文摘BACKGROUND Visceral leishmaniasis(VL)is a systemic protozoan infection caused by Leishmania donovani(L.donovani)and transmitted by sand flies,causing macrophage invasion in the liver,spleen,and bone marrow.Diagnosis of VL is currently based on clinical signs,symptoms,and specific in-vitro markers and bone marrow investigations.However,VL's specific hematological and bone marrow manifestation in Sudanese pediatric patients is not well studied.AIM To examine the blood and bone marrow characteristics in pediatric patients from Sudan who have VL.METHODS This is a retrospective hospital-based study with a sample of 107 consecutive Sudanese pediatric patients.The data focused on hematological and bone marrow results.We included only the completed records of the pediatric patients with VL in the Tropical Disease Teaching Hospital in Khartoum,Sudan from the period of 2016 to 2020.RESULTS The majority of pediatric patients included in this study are below 5-years-old(n=59,55.2%).Moreover,anemia,thrombocytopenia,and leukopenia were among the prevalent characteristics in the population under study.To further analyze the data,we developed a machine learning model using boosted forest algorithms to predict L.donovani parasites load,with a mean accuracy of 0.88 for the training dataset and an accuracy of 0.46,0.50,and 0.74 for mild,moderate,and severe L.donovani parasite load in the validation dataset.CONCLUSION This study shows that the most common bone marrow change among Sudanese VL children was increased chronic inflammatory cells(n=88,82.2%)with present macrophage hemophagocytes(n=103,96.3%).While anemia and thrombocytopenia were the most common hematological changes.These results will hopefully lead to an early diagnosis and hence better management for Sudanese pediatric patients with suspected VL.
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.
基金National Natural Science Foundation of China(No.82370164)Sanming Project of Medicine in Shenzhen(No.SZSM202011004)Shenzhen Science and Technology Innovation Commission(JCYJ20180307150419435 and JCYJ20210324123004011).
文摘Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.
文摘In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.
文摘Patients with hematological tumors experience physical and psychological stress,and negative psychological states.Baduanjin,an emerging psychological rehabil-itation method combined with resistance exercise,has received widespread attention.This study reviews the current status of the application of Baduanjin combined with resistance exercise in improving the negative psychological state of patients with hematological tumors and discusses its problems and prospects.Through a literature review and comprehensive analysis,the application of Baduanjin and resistance exercise in the psychological rehabilitation of patients with hematological tumors was identified and evaluated.The results showed that Baduanjin with resistance exercise had a positive effect on improving negative psychological states of patients with hematological tumors,which can alleviate anxiety,depression,and other adverse emotions,and improve quality of life.However,there is a lack of unified and standardized exercise intervention programs for practical application,and patient participation and compliance must be improved.Baduanjin combined with resistance exercise can potentially improve the negative psychological status of patients with hematological tumors;however,it is still necessary to further standardize and improve the exercise program improving patient participation and compliance.Future studies should strengthen theoretical exploration and empirical research,providing more effective psychological rehabilitation strategies for patients with hematological tumors.
文摘Background: Hemopathies were rarely observed in major sickle cell disease patients some thirty years ago, probably due to the high mortality rate among the latter as a result of progressive complications. Thanks to advances in the management of sickle cell disease, patients' life expectancy has increased considerably, exposing them more frequently to neoplasia, including hematological malignancies. The increased risk of leukemogenesis is multifactorial and linked to the pathophysiological mechanisms of the clinical manifestations of sickle cell disease. Study Setting: The clinical haematology department of campus teaching hospital and the paediatric onco-haematology unit of Sylvanus Olympio teaching hospital in Lomé were used as study settings. Observations: Four hematologic malignancies were collected in a cohort of 5847 major sickle cell syndromes. The median age of the patients was 31.25 years (extremes: 14 and 58 years) and they were predominantly female (sex ratio M/F = 0.25). Two were on background therapy with hydroxyurea. Among the four patients, there were two cases of acute lymphocytic leukemia, including ALL3 in a 58-year-old SS woman and T-ALL2 in a 12-year-old SC. Then, a case of lymphocytic lymphoma in a 20-year-old SS man was reported and finally a case of chronic myelocytic leukemia in a 33-year-old woman of Sβ+ thalassaemia phenotype. Conclusion: To further report this coexistence, it is therefore essential to systematically consider hematological malignancies during major sickle cell syndromes even if there are similarities in the symptomatology of these two serious pathological situations.
文摘Research Background: Malaria, predominantly caused by Plasmodium falciparum, continues to be a leading cause of morbidity and mortality among children under five years of age in sub-Saharan Africa. Malaria remains a significant public health challenge in Nigeria, particularly in regions where access to healthcare facilities is limited. Home-based management of malaria has emerged as a critical strategy to reduce disease burden, enabling timely treatment at the community level. Chloroquine, once the cornerstone of malaria treatment, is still utilized in some settings due to its affordability, availability, oral administration, and historical effectiveness against Plasmodium species. However, the widespread emergence of chloroquine-resistant strains of Plasmodium falciparum has necessitated a reevaluation of its role in malaria management. This study investigates the therapeutic effectiveness of oral chloroquine in home-based management, focusing on its ability to reduce parasitemia and alleviate clinical symptoms. Additionally, the study assessed the influence of protein nutritional status and bacterial/viral co-infections on malaria outcomes among children under five years in Jos, Nigeria, providing insights into its current relevance in resource-limited settings. Research Objective: Given the historical use of chloroquine and emerging reports of chloroquine-sensitive strains, this research aims to evaluate the therapeutic effectiveness of oral chloroquine in the home-based management of childhood malaria in Jos, Nigeria, by assessing its impact on parasitemia, symptom alleviation, biochemical and hematological profiles, nutritional status, and interactions with co-infections while providing evidence-based insights to inform policy, community health practices, and contemporary malaria control strategies. Methods: This cross-sectional and analytical study evaluated the role of oral chloroquine in the home-based management of childhood malaria in Jos, Nigeria. A total of 93 children under five years of age, presenting with fever and confirmed Plasmodium falciparum parasitemia, were recruited from two hospitals in Jos. Participants were stratified into three groups: children treated with chloroquine at home prior to hospital presentation, untreated children with uncomplicated malaria, and untreated children with severe malaria. Caregivers were surveyed to assess the use of chloroquine as a first-line home treatment, including dosage and timing of administration. Ethical approval was obtained from the Jos University Teaching Hospital (JUTH) Ethical Committee, and informed consent was secured from caregivers before sample collection and interviews. Parasitemia levels were measured to correlate parasite density with clinical outcomes. Comprehensive assessments included biochemical analysis of serum creatinine, liver enzymes, and protein levels to evaluate organ function and metabolic status. Hematological parameters, including hemoglobin concentration and red blood cell (RBC) count, were measured to assess malaria severity and anemia. Nutritional status was evaluated through anthropometric measurements and serum protein analyses. Co-infections with bacterial and viral pathogens were identified using microscopic examination of blood samples. Statistical analyses were performed to identify significant associations between chloroquine treatment, clinical outcomes, and biochemical indicators. Results: Children treated with chloroquine demonstrated significantly lower parasitemia levels (18.13%) compared to untreated children with uncomplicated malaria (34.35%) and those with severe malaria (43.57%). Hemoglobin levels were notably higher in the chloroquine-treated group (9.60 g/dL) compared to the untreated groups, indicating a reduced burden of malaria-induced anemia. Body temperatures were significantly lower among chloroquine-treated children, underscoring its efficacy in fever reduction. Bacterial co-infections were identified in 54.35% of malaria cases, emphasizing their role in exacerbating disease severity. Liver and kidney function tests revealed no significant differences between the groups, indicating that chloroquine treatment did not result in hepatic or renal toxicity. Additionally, all participants exhibited adequate nutritional status, with no evidence of protein-energy malnutrition. Conclusion: The findings of this study highlight the significant role of oral chloroquine in the home-based management of childhood malaria in Jos, Nigeria. Children treated with chloroquine exhibited substantially lower parasitemia levels and higher hemoglobin concentrations compared to untreated children, demonstrating its effectiveness in reducing parasite burden and mitigating malaria-induced anemia. Additionally, chloroquine treatment was associated with lower body temperatures, reflecting its efficacy in fever control. Bacterial co-infections were present in over half of the malaria cases (54.35%), underscoring their potential contribution to disease severity and the need for integrated management strategies. Importantly, liver and kidney function tests showed no significant differences among the groups, indicating that chloroquine use did not lead to hepatic or renal toxicity. Furthermore, all participants maintained adequate nutritional status, with no signs of protein-energy malnutrition. These results support the continued use of chloroquine as a viable option in the home-based management of uncomplicated malaria while highlighting the importance of addressing co-infections to improve clinical outcomes.
