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Introduction: Daratumumab, lenalidomide, and dexamethasone (DRd) and bortezomib, lenalidomide, and dexamethasone (VRd) are the only preferred treatment regimens for patients with transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM). As there are no randomized head-to-head studies of DRd versus VRd, this analysis aimed to compare real-world time-to-next-treatment (TTNT) or death in this population., Methods: Patients with NDMM who received front-line (FL) DRd or VRd were identified from the Acentrus database (January 1, 2018 to May 31, 2023). Those with a record of a stem cell transplant or aged < 65 years were excluded to limit analysis to the TIE population. Inverse probability of treatment weighting was used to balance baseline patient characteristics. A doubly robust Cox proportional hazards model was used to compare TTNT or death between cohorts., Results: A total of 149 and 494 patients who initiated DRd and VRd, respectively, were identified. After weighting (weighted N DRd  = 302, weighted N VRd  = 341), cohorts had similar baseline characteristics. Of these, 98 (32.4%) DRd and 175 (51.2%) VRd patients either received a subsequent line of therapy or died, with a median TTNT or death of 37.8 months in the DRd cohort and 18.7 months in the VRd cohort (hazard ratio: 0.58, 95% confidence interval: 0.35, 0.81; p < 0.001)., Conclusion: Treatment of TIE NDMM patients with DRd led to a significantly longer TTNT or death compared to VRd, evidenced by a 42% risk reduction, supporting the effectiveness of DRd over VRd as FL treatment in this patient population., (© 2024 Janssen Scientific Affairs, LLC. Cancer Medicine published by John Wiley & Sons Ltd.)

Aims: Krüppel-like factor 1 (KLF1) is an erythroid-specific transcription factor playing an important role in erythropoiesis and haemoglobin (Hb) switching. Biallelic KLF1 mutations can cause haemolytic anaemia with thalassaemia-like syndromes but are rarely reported. We explore the KLF1 mutations in Thai subjects with unexplainable haemolytic anaemia., Methods: The study was done on 57 subjects presented with haemolytic anaemia and elevated Hb F without β-thalassaemia diseases. Hb analysis was performed using capillary electrophoresis. Analyses of α-thalassaemia, β-thalassaemia and KLF1 genes were performed using PCR-based methods and DNA sequencing., Results: Thirteen subjects with compound heterozygous for a known and five new genetic KLF1 interactions were identified, including KLF1:c.519&#95;525dupCGGCGCC/c.892G>C with class 3/2 (n=8), and each subject with new genetic interaction, including KLF1:c.-154C>T;643C>T/c.983G>A with class 3/2, KLF1:c.-154C>T;643C>T/c.809C>G with class 3/2, KLF1:c892G>C/c.983G>A with class 2/2, KLF1:c.892G>C/c.1001C>G with class 2/2 and KLF1:c.1001C>G/c.1003G>A with class 2/2. Most of them had anaemia with Hb levels ranging from 45 to 110 g/L, hypochromic microcytosis, aniso-poikilocytosis, increased Hb F levels (17.9%-47.4%), small amounts of Hb Bart's, regular blood transfusion, hyperbilirubinaemia, increased serum ferritin and nucleated red blood cell., Conclusions: Biallelic KLF1 mutations associated with anaemia may not be uncommon in Thailand. Characteristics of haemolytic anaemia, abnormal red cell morphology with nucleated red blood cells and elevated Hb F, and presenting small amounts of Hb Bart's without thalassaemia diseases are useful markers to further investigation of the KLF1 gene., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

There is no consensus to support the single unit-transfusion policy (1-RBC) over the double-unit transfusion policy (2-RBC) in patients with hematological disorders undergoing chemotherapy or stem cell transplantation. We searched PubMed, Embase, and Cochrane Library. Risk ratios (RR) and mean differences (MD) were pooled. Statistical analysis was performed using Review Manager and R software. Heterogeneity was assessed using I 2 statistics. Hemoglobin (Hb) levels at discharge (MD -0.41 g/dL; 95% CI -0.53, -0.29 g/dL; P < .01) and total RBC units used per admission (MD -0.82 units; 95% CI -1.60, -0.05 units; P = .04) were significantly lower in patients who received 1-RBC, while length of hospital stay (MD 0.05 days; 95% CI -0.29, 0.39 days; P = .89), severe bleeding (RR 1.52; 95% CI 0.85, 2.71; P = .16) and mortality (RR 0.89; 95% CI 0.52, 1.53; P = .69) showed no significant difference between groups. In patients with hematological disorders undergoing chemotherapy or stem cell transplantation, 1-RBC is associated with lower Hb levels at discharge and a reduction in the total number of RBC units used per admission, with no significant difference in terms of length of hospital stay, severe bleeding risk, transfusion-related adverse events and mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Thalassemia is a hereditary blood disorder that poses significant challenges for affected children and their families. Caregivers, particularly mothers, often experience difficulties in managing their child's condition. Understanding their current experience is crucial for improving care and support., Objective: This study aimed to explore the experiences of mothers caring for children with thalassemia in Banten, Indonesia., Methods: A qualitative descriptive approach was employed, involving semi-structured in-depth interviews with eleven mothers of children diagnosed with thalassemia. Data were collected from April to May 2023. The interviews were audio recorded, and the data were analyzed verbatim using Colaizzi's method to identify key themes related to the experiences., Results: Three themes were developed: 1) Perception of thalassemia as a genetic condition, 2) Emotional, logistical, and practical caregiving challenges, and 3) Support received by mothers in caring for children with thalassemia., Conclusion: The findings highlight the multifaceted challenges faced by mothers of children with thalassemia and emphasize the need for improved communication, emotional support, and care coordination from nurses and healthcare providers. Future research should focus on expanding support systems and exploring effective interventions to enhance the quality of life for families navigating the complexities of chronic illness., Competing Interests: The authors declared no conflict of interest., (© The Author(s) 2024.)

Non-Hodgkin lymphoma (NHL) is one of the most common hematological cancers in the United States. The mortality rate of NHL in the United States is the sixth highest among all cancers. Our cross-sectional study aims to examine the trends and disparity in NHL mortality. We analyzed death certificate data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) United States to determine the NHL mortality trends among the U.S. population aged ≥15 years. NHL (ICD-10 C82-85) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and joinpoint trend analysis were performed to determine the average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, NHL accounted for 457,143 deaths in the United States, of which 54% are men and 46% are women. The NHL AAMR decreased significantly from 10.59 to 6.21 per 100,000 individuals with an AAPC of -2.55. Men had a higher AAMR than women (10.10 vs 6.29 per 100,000 individuals). Whites recorded the highest AAMR (8.43 per 100,000 individuals), followed by Hispanics (6.32 per 100,000 individuals), Blacks (5.71 per 100,000 individuals), American Indians (5.31 per 100,000 individuals), and Asians (5.10 per 100,000 individuals). Those who lived in the Midwest and the rural areas had the highest AAMR at 8.60 and 8.35 per 100,000 individuals respectively. Despite the declining NHL mortality rate, this study calls for targeted intervention to improve outcomes for susceptible individuals affected by NHL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Peripheral T-cell lymphoma (PTCL) is an extensive class of heterogeneous diseases with dismal outcomes. Brentuximab vedotin (BV) is an antibody‒drug conjugate (ADC) comprising CD30-directed antibody. This review aimed to evaluate the efficacy and safety of BV for treating PTCL. We searched the PubMed, Embase, Cochrane Library and Web of Science databases for studies evaluating the efficacy of BV alone or in combination with other drugs for treating PTCL. The primary outcome measures included objective response rate (ORR), complete remission (CR), progression-free survival (PFS) and overall survival (OS). The secondary outcomes included 5-year OS, 5-year PFS and adverse events. 22 studies involving 1137 patients were included. These studies reported the use patterns of BV, ORR, CR, PFS, OS, and adverse events. The pooled ORR and CR rate were 68% (95% CI: 59%-75%) and 43% (95% CI: 34%-53%). For survival outcomes, the longest median PFS was 8.3 months, and the longest median OS was 26.3 months. The most common adverse event was peripheral neuropathy and neutropenia. The analysis suggested that BV alone or in combination with other drugs improved the response and survival rates in PTCL patients and was associated with tolerable adverse effects.

Objective: To investigate the benefits of menstrual management in women undergoing hematopoietic stem cell transplantation (HSCT), in whom heavy menstrual bleeding (HMB) can be an underestimated bleeding complication., Methods: This was a retrospective cohort study. Patients who had undergone HSCT in the Gynecological Endocrinology Clinic of Peking University People's Hospital were included over 10 years. The data of hematology and menstruation for all participants were collected. The management methods of the intervention group include gonadotropin-releasing hormone agonists (GnRHa), combined oral contraceptives (COC), or low-dose mifepristone. Patients who did not receive management were included in the control group., Results: There were 112 patients included in the intervention group and 218 patients included in the control group. In all, 90.0%(297/330) of patients presented with HMB before HSCT. In the control group, 83.5%(182/218) of patients experienced menstruation in the laminar air-flow room (LAFR), whereas only 22.3%(25/112) did in the intervention group. After leaving the LAFR, the incidence of recurrent uterine bleeding was significantly reduced in the intervention group (17.9%(20/112/) versus 50.9%(111/218), p < 0.001). Patients who did not undergo menstrual management had a higher risk of bleeding than those who did (odds ratio 18.12, p < 0.001)., Conclusion: Menstrual management significantly reduces the incidence of HMB in HSCT patients and acts as a protective factor to prevent menstrual bleeding in the LAFR., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Introduction: High-risk febrile neutropenia (FN) is one of the main causes of morbidity and mortality in onco-hematology. The initiation of empirical antibiotic therapy is an emergency that can change the prognosis of some patients. Given the emergence of increasingly resistant Gram-positive bacteremia, glycopeptides, as an empirical treatment, have an important place in the management of high-risk FN. The aim of this study is to evaluate the appropriateness of glycopeptide prescription in high-risk FN patients., Methods: This study was conducted in the Hematology Department of Fattouma Bourguiba University Hospital of Monastir, Tunisia. Patients with high-risk FN were enrolled during the period between January 1 and December 31, 2020., Results: Of the 29 patients included in this study, 88 FN episodes were noted of which 39 episodes treated with glycopeptides were evaluated. Twenty-four febrile episodes were empirically treated with glycopeptides (27.3%) of which 17 prescriptions (70.8%) were appropriate according to the European Conference on Infection in Leukemia and the Infectious Diseases Society of America recommendations. A therapeutic escalation using glycopeptides was noted in 17% of cases and appropriately opted in 6 FN episodes (40%)., Conclusion: Prescriptions of glycopeptides were appropriate according to the international recommendations in 71% of the empirical prescriptions and in 40% of the therapeutic escalation using glycopeptides. In high-risk FN episodes, glycopeptides prescriptions should be rationalized and limited to the indications detailed in the international guidelines to control the emergence of multidrug-resistant bacteria., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Malaria, a parasitic infection caused by the genus Plasmodium, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms, and blood analysis plays a crucial role in determining the appropriate treatment approach. This study discusses various hematologic complications associated with different Plasmodium species. A review of scientific databases including PubMed, Science Direct, Web of Science, Scopus, EMBASE, Magiran, SID, IranMedex was conducted using standard keywords such as Plasmodium, malaria, anemia and blood disorders (hematologic disorder) between 2000 and 2024. The review focused on articles pertaining to clinical trials, prospective cohort, retrospective, cross-sectional and case-control studies. Articles evaluating the effects of malaria on blood cells and indices, with target groups including human and animals, were included. Articles not written in English or Farsi were excluded. Our review revealed that, apart from iron deficiency anemia and vascular dysfunction contributed in part by adhesion of infected RBC to endothelium, decreases in hematocrit and hemoglobin levels, as part of pancytopenia and thrombocytopenia, are characteristic of Plasmodium infection. Additionally, the occurrence of inflammation due to the release of inflammatory cytokines and complement activation can complicate the clinical features of malaria in individuals with hematologic conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Myelofibrosis (MF), a complex hematological malignancy, presents a diverse array of symptoms, including anemia, constitutional symptoms, bone marrow insufficiency, and splenomegaly. The latter, often necessitating blood transfusions, poses an essential obstacle to MF management. While conventional approaches predominantly involve the use of JAK inhibitors, the potential for exacerbating anemia introduces complexity to the treatment. Nonetheless, Momelotinib stands out as a promising pharmaceutical compound with the potential to revolutionize the field. Momelotinib is an ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes. By targeting MF's hematological and fibrotic aspects, Momelotinib influences iron metabolism by regulating hepcidin. This results in reduced hepcidin expression and increased iron availability, ultimately leading to improved anemia and reduced dependency on blood transfusion. This study aims to provide a concise overview of the pathogenesis of MF and elucidate the mechanism of action of Momelotinib. Subsequently, our review offers a practical summary encompassing the effects of Momelotinib in monotherapy, combined comparative drug therapy, and its associated side effects. Additionally, we explore the application of Momelotinib in other cancer types and investigate predictors for treatment success. Furthermore, we examine the utilization of Momelotinib in patients with liver and kidney failure., (© 2024. The Author(s).)

Aims: To explore the clinical and pathological features of light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-LC)., Methods: From January 2010 to December 2022, patients who were diagnosed with PGNMID-LC were selected, and their clinical and pathological features were retrospectively analysed., Results: Three males aged 42-61 years old were enrolled. Hypertension was present in three patients, oedema in three patients, anaemia in two patients, proteinuria in three patients, nephrotic syndrome in one patient, microscopic haematuria in three patients, renal insufficiency in two patients and hypocomplementaemia of C3 in one patient. Elevated serum-free LC ratios and plasmacytosis on bone marrow smears were observed in three patients, and κ was identified by serum protein immunofixation electrophoresis in one patient. Renal biopsy showed membranoproliferative glomerulonephritis in two patients and endocapillary proliferative glomerulonephritis in one patient on light microscopy. Immunofluorescence indicated restricted κ LC and C3 distributed in glomeruli. By electron microscopy, electron-dense deposits without substructure were identified predominantly in the mesangial and subendothelial regions and were variable in the subepithelial region. Two patients were treated with plasma cell-directed chemotherapy and achieved haematological complete response or very good partial response, and one of them achieved a renal status of complete remission. One patient treated with immunosuppressive therapy only did not achieve haematological or renal remission., Conclusions: PGNMID-LC is a rare and uniform disease with a high frequency of a detectable pathogenic plasma cell clone and is characterised by glomerular deposition of restricted LC and C3 in renal pathology. Plasma cell-directed chemotherapy may improve haematological and renal prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Accumulated evidence emerges that dynamic changes in human gut microbiota and microbial metabolites can alter the ecological balance of symbiotic hosts. The gut microbiota plays a role in various diseases through different mechanisms. More and more attention has been paid to the effects that human microbiota extends beyond the gut. This review summarized the current understanding of the roles that gut microbiota plays in hematopoietic regulation and the occurrence and development of benign and malignant hematologic diseases. The progress of the application of microbiota in treatment was discussed in order to provide new insights into clinical diagnosis and treatment in the future., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).)

Corynebacterium is generally considered a contaminant in clinical practice. However, it may cause bacteremia in patients with hematologic disorders, and factors that contribute to its mortality are unclear. A case series and systematic literature review identified 96 cases of Corynebacterium bacteremia inhematologic disorderpatients. The median age was 50.5 years (range: 2-93 years), with 79 (82%) patients 18 years or older, and 64 (67%) patients male. Most cases involved hematologic malignancies, and neutropenia was observed in approximately 75% cases. The most common sites of infection/symptoms were skin and soft tissue, respiratory, and catheter-related bloodstream infection. The infection-related mortality was 23%, and univariate analysis showed that age, respiratory infection/symptoms, and source control were significantly associated with infection-related mortality. Multivariate analysis indicates that infection-related mortality was significantly reduced by source control (OR: 0.24, 95% CI: 0.06-0.97, p  = 0.046). Therefore, when Corynebacterium infections are suspected, early source control should be considered.

Background: The MC-80 (Mindray, Shenzhen, China), a newly available artificial intelligence (AI)-based digital morphology analyzer, is the focus of this study. We aim to compare the leukocyte differential performance of the Mindray MC-80 with that of the Sysmex DI-60 and the gold standard, manual microscopy., Methods: A total of 100 abnormal peripheral blood (PB) smears were compared across the MC-80, DI-60, and manual microscopy. Sensitivity, specificity, predictive value, and efficiency were calculated according to the Clinical and Laboratory Standards Institute (CLSI) EP12-A2 guidelines. Comparisons were made using Bland-Altman analysis and Passing-Bablok regression analysis. Additionally, within-run imprecision was evaluated using five samples, each with varying percentages of mature leukocytes and blasts, in accordance with CLSI EP05-A3 guidelines., Results: The within-run coefficient of variation (%CV) of the MC-80 for most cell classes in the five samples was lower than that of the DI-60. Sensitivities for the MC-80 ranged from 98.2% for nucleated red blood cells (NRBC) to 28.6% for reactive lymphocytes. The DI-60's sensitivities varied between 100% for basophils and reactive lymphocytes, and 11.1% for metamyelocytes. Both analyzers demonstrated high specificity, negative predictive value, and efficiency, with over 90% for most cell classes. However, the DI-60 showed relatively lower specificity for lymphocytes (73.2%) and lower efficiency for blasts and lymphocytes (80.1% and 78.6%, respectively) compared with the MC-80. Bland-Altman analysis indicated that the absolute mean differences (%) ranged from 0.01 to 4.57 in MC-80 versus manual differential and 0.01 to 3.39 in DI-60 versus manual differential. After verification by technicians, both analyzers exhibited a very high correlation (r = 0.90-1.00) with the manual differential results in neutrophils, lymphocytes, and blasts., Conclusions: The Mindray MC-80 demonstrated good performance for leukocyte differential in PB smears, notably exhibiting higher sensitivity for blasts identification than the DI-60., (© 2024 John Wiley & Sons Ltd.)

Periodontitis is a common oral condition that can have a significant impact on the overall health of the body. In recent years, attention has been paid to potential relationships between periodontitis and various hematological disorders. This publication aims to present information available in the literature on this relationship, focusing on examples of red blood cell disorders (such as aplastic anemia and sickle cell anemia) and white blood cell disorders (such as cyclic neutropenia, maladaptive trained immunity, clonal hematopoiesis, leukemia, and multiple myeloma). Understanding these associations can help physicians and dentists better diagnose, monitor, and treat patients associated with both groups of conditions, highlighting the need for interdisciplinary care for patients with oral disorders and hematologic diseases.

Background: The underlying biology of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) is not fully elucidated, and the extent of its overlap with acute graft-versus-host disease (aGvHD) remains unclear. In order to establish potential indicator to distinguish ES more accurately, we conducted a retrospective analysis of cytokine levels during HSCT., Methods: A total of 121 consecutive adult patients who underwent HSCT were enrolled in this study. Blood samples for interleukin (IL)-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-1β, IL-12p70, interferon (IFN)-γ, IFN-α, tumor necrosis factor alpha (TNF-α) and C-reactive protein CRP were regularly assessed after transplantation and during transplantation related adverse events. Additionally, the balance of naïve, central memory and effector memory of CD4 + and CD8 + was analyzed around 30 and 60 days after stem cell infusion, respectively., Results: Thirty (24.79 %) and 33 (27.27 %) patients were diagnosed with ES and aGvHD, respectively. ES was characterized by a significant increase in level of IL-5, IL-6, IL-8 and sIL-2R, while aGvHD was associated with a significant upregulation of IL-6, IL-5, IL-10 and sIL-2R in the patients from grade I to grade IV. Notably, patients got much higher levels of IL-6, IL-5 and sIL-2R when developed to ES than to aGvHD. Moreover, a pronounced shift from naïve to memory cells, both in CD4 + and CD8 + subsets, was found in ES patients., Conclusions: These findings suggest that cytokine profiles could serve as potential indicators for detecting and differentiating ES and aGvHD, enabling timely clinical intervention. Prospective clinical trials involving larger, independent patient cohorts are required to validate these observations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs., Methods: MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes., Results: Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCA A1219GfsTer59 variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes., Conclusions: Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Individuals with Kabuki syndrome present with immunodeficiency; however, how pathogenic variants in the gene encoding the histone-modifying enzyme lysine methyltransferase 2D (KMT2D) lead to immune alterations remain poorly understood. Following up on our prior report of KMT2D-altered integrin expression in B-cells, we performed targeted analyses of KMT2D's influence on integrin expression in T-cells throughout development (thymocytes through peripheral T-cells) in murine cells with constitutive- and conditional-targeted Kmt2d deletion. Using high-throughput RNA-sequencing and flow cytometry, we reveal decreased expression (both at the transcriptional and translational levels) of a cluster of leukocyte-specific integrins, which perturb aspects of T-cell activation, maturation, adhesion/localization, and effector function. H3K4me3 ChIP-PCR suggests that these evolutionary similar integrins are under direct control of KMT2D. KMT2D loss also alters multiple downstream programming/signaling pathways, including integrin-based localization, which can influence T-cell populations. We further demonstrated that KMT2D deficiency is associated with the accumulation of murine CD8 + single-positive (SP) thymocytes and shifts in both human and murine peripheral T-cell populations, including the reduction of the CD4 + recent thymic emigrant (RTE) population. Together, these data show that the targeted loss of Kmt2d in the T-cell lineage recapitulates several distinct features of Kabuki syndrome-associated immune deficiency and implicates epigenetic mechanisms in the regulation of integrin signaling., Competing Interests: AB is a cofounder of Datirium, the developer of Scientific Data Analysis Platform https://SciDAP.com used here for processing RNA-Seq data. AB and MK developed CWL-Airflow licensed to Datirium, LLC. AL is an employee of Amgen Inc. HB is a consultant for Mahzi therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Potter, Zhang, Kotliar, Wu, Schafer, Stefan, Boukas, Qu’d, Bodamer, Simpson, Barski, Lindsley and Bjornsson.)

Background: In Vietnam, a lack of evidence about the unexpected antibodies hinders the capabilities to prepare the necessary resources and personnel for treating patients with blood disorders. This study aimed to measure the rates of different unexpected antibodies in patients having blood orders in Vietnam., Study Design and Methods: A cross-sectional study was conducted at the National Institute of Hematology - Blood Transfusion, Vietnam on 5608 patients with blood disorders. Information was obtained from the medical records, blood transfusion forms, screening test forms., Results: The prevalence rate of unexpected antibodies in patients with haematological disorders was 9.3%. The most prevalent occurrence was the presence of an atypical antibody type, accounting for 61% of patients. The co-occurrence of this atypical antibody type and other types of antibodies was also observed, with the respective occurrence rates of 23.9%, 10.1%, 3.8%, and 1.2% for the combination of two, three, four, and five unexpected antibody types. The presence of one type of unexpected antibody was predominant, namely anti-E, accounting for the highest proportion (32.9%), followed by anti-Mia (18.4%). Among the 125 patients, the most frequently observed combination of abnormal antibodies was anti-E with anti-c (14.3%) and anti-E with anti-Mia (3.4%). Among the cohort of 53 patients exhibiting three types of unexpected antibodies, the most prevalent combination observed was anti-c, anti-E, and anti-Mia (5.7%)., Conclusion: This study revealed a prevalence rate of 9.3% in the presence of unexpected antibodies in patients with blood disorders. The occurrence of individual unexpected antibodies surpasses that of coordinated antibodies., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: Vaccination against SARS-CoV-2 in immunocompromised patients with hematologic malignancies (HM) is crucial to reduce the severity of COVID-19. Despite vaccination efforts, over a third of HM patients remain unresponsive, increasing their risk of severe breakthrough infections. This study aims to leverage machine learning's adaptability to COVID-19 dynamics, efficiently selecting patient-specific features to enhance predictions and improve healthcare strategies. Highlighting the complex COVID-hematology connection, the focus is on interpretable machine learning to provide valuable insights to clinicians and biologists., Methods: The study evaluated a dataset with 1166 patients with hematological diseases. The output was the achievement or non-achievement of a serological response after full COVID-19 vaccination. Various machine learning methods were applied, with the best model selected based on metrics such as the Area Under the Curve (AUC), Sensitivity, Specificity, and Matthew Correlation Coefficient (MCC). Individual SHAP values were obtained for the best model, and Principal Component Analysis (PCA) was applied to these values. The patient profiles were then analyzed within identified clusters., Results: Support vector machine (SVM) emerged as the best-performing model. PCA applied to SVM-derived SHAP values resulted in four perfectly separated clusters. These clusters are characterized by the proportion of patients that generate antibodies (PPGA). Cluster 1, with the second-highest PPGA (69.91%), included patients with aggressive diseases and factors contributing to increased immunodeficiency. Cluster 2 had the lowest PPGA (33.3%), but the small sample size limited conclusive findings. Cluster 3, representing the majority of the population, exhibited a high rate of antibody generation (84.39%) and a better prognosis compared to cluster 1. Cluster 4, with a PPGA of 66.33%, included patients with B-cell non-Hodgkin's lymphoma on corticosteroid therapy., Conclusions: The methodology successfully identified four separate patient clusters using Machine Learning and Explainable AI (XAI). We then analyzed each cluster based on the percentage of HM patients who generated antibodies after COVID-19 vaccination. The study suggests the methodology's potential applicability to other diseases, highlighting the importance of interpretable ML in healthcare research and decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This article discusses the orofacial clinicoradiographic features of systemic diseases that manifest in the orofacial region. The systemic diseases discussed are grouped into the following: autoimmune diseases, endocrine diseases, bone diseases, hematologic diseases, syndromes, and malignancies. The radiographic manifestation ranges from radiolucent bony destruction, increased bone density, calcification, thinning of cortical plate, loss of trabeculation, missing teeth, and supernumerary teeth. It is imperative for clinicians to be cognizant of these findings, as they may be the first manifestation of these systemic diseases., Competing Interests: Disclosure All authors declare that there are no financial conflicts associated with this study and that the funding source has no role in conceiving and performing the study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: To develop and internally validate a prediction model for identifying patients with hematologic diseases of fall risk., Research Design and Methods: This is a prospective cohort study from a prospective collection of data for 6 months. We recruited 412 patients with hematologic diseases in medical institutions and home environment of China. The outcome of the prediction model was fall or not. These variables were filtered via univariable logistic analysis, LASSO, and multivariable logistic analysis. We adopt an internal validation method of K-fold cross validation. The area under the ROC curve and the H-L test were used to evaluate the discrimination and calibration of the model., Results: Five influencing factors were identified multivariable logistic regression analysis. The established model equation is as follows: the H-L goodness-of-fit test of the model p  > 0.05. The area under the ROC curve of train is 0.957 (95% CI: 0.936 ~ 0.978), and the area under the ROC curve of test is 0.962 (95% CI: 0.884 ~ 1), so the model calibration and discriminant validity are good., Conclusion: Our equation has good sensitivity and specificity in predicting the fall risk of patients with hematologic diseases, and has certain positive significance for clinical assessment of their fall risk., Trial Registration Number: ChiCTR2200063940.

Objective: To investigate the quality of life (QoL) and the impact of caregiving in family caregivers of hematological cancer patients and its association with patient symptom burden., Methods: A cross-sectional study including Danish patients (n = 375) and caregivers (n = 140). Caregivers completed scales for anxiety and depression using the Hospital Anxiety and Depression Scale, sleep quality using the Pittsburgh Sleep Quality Index, health related QoL using the 12-item Short-Form Health Survey, and caregiver roles using the Caregiver Roles and Responsibilities Scale. Patients reported symptoms using the MD Anderson Symptom Inventory. Analysis of covariance was used to examine associations between patient symptom burden and caregivers' QoL outcomes., Results: The results show that caregivers experience sleep difficulties, moderate anxiety, and reduced QoL. Patient symptom burden was significantly associated with caregiver anxiety (p = 0.009), and mental well-being (p = 0.002), while patient treatment status was a significant factor associated with caregiver anxiety (p = 0.016), depression (p = 0.009), emotional well-being (p = 0.002), and sleep (p = 0.01)., Conclusion: Caregivers of patients with hematological cancers undergoing active treatment face a high symptom burden, which significantly impacts their QoL, including sleep, psychological well-being, and emotional health. Patients reported a high symptom burden, and patient symptom burden was significantly associated with caregiver QoL. Adequate patient and caregiver support is needed to promote their well-being and mitigate adverse health effects in caregivers, and this should be acknowledged in the context of caring for patients with hematological cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene., Methods: A child diagnosed with KS at the Fujian Children's Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis., Results: The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PS2+PM2&#95;Supporting)., Conclusion: The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.

Importance: The lack of standardized genetics training in pediatrics residencies, along with a shortage of medical geneticists, necessitates innovative educational approaches., Objective: To compare pediatric resident recognition of Kabuki syndrome (KS) and Noonan syndrome (NS) after 1 of 4 educational interventions, including generative artificial intelligence (AI) methods., Design, Setting, and Participants: This comparative effectiveness study used generative AI to create images of children with KS and NS. From October 1, 2022, to February 28, 2023, US pediatric residents were provided images through a web-based survey to assess whether these images helped them recognize genetic conditions., Interventions: Participants categorized 20 images after exposure to 1 of 4 educational interventions (text-only descriptions, real images, and 2 types of images created by generative AI)., Main Outcomes and Measures: Associations between educational interventions with accuracy and self-reported confidence., Results: Of 2515 contacted pediatric residents, 106 and 102 completed the KS and NS surveys, respectively. For KS, the sensitivity of text description was 48.5% (128 of 264), which was not significantly different from random guessing (odds ratio [OR], 0.94; 95% CI, 0.69-1.29; P = .71). Sensitivity was thus compared for real images vs random guessing (60.3% [188 of 312]; OR, 1.52; 95% CI, 1.15-2.00; P = .003) and 2 types of generative AI images vs random guessing (57.0% [212 of 372]; OR, 1.32; 95% CI, 1.04-1.69; P = .02 and 59.6% [193 of 324]; OR, 1.47; 95% CI, 1.12-1.94; P = .006) (denominators differ according to survey responses). The sensitivity of the NS text-only description was 65.3% (196 of 300). Compared with text-only, the sensitivity of the real images was 74.3% (205 of 276; OR, 1.53; 95% CI, 1.08-2.18; P = .02), and the sensitivity of the 2 types of images created by generative AI was 68.0% (204 of 300; OR, 1.13; 95% CI, 0.77-1.66; P = .54) and 71.0% (247 of 328; OR, 1.30; 95% CI, 0.92-1.83; P = .14). For specificity, no intervention was statistically different from text only. After the interventions, the number of participants who reported being unsure about important diagnostic facial features decreased from 56 (52.8%) to 5 (7.6%) for KS (P < .001) and 25 (24.5%) to 4 (4.7%) for NS (P < .001). There was a significant association between confidence level and sensitivity for real and generated images., Conclusions and Relevance: In this study, real and generated images helped participants recognize KS and NS; real images appeared most helpful. Generated images were noninferior to real images and could serve an adjunctive role, particularly for rare conditions.

In standard hospital blood tests, the traditional process requires doctors to manually isolate leukocytes from microscopic images of patients' blood using microscopes. These isolated leukocytes are then categorized via automatic leukocyte classifiers to determine the proportion and volume of different types of leukocytes present in the blood samples, aiding disease diagnosis. This methodology is not only time-consuming and labor-intensive, but it also has a high propensity for errors due to factors such as image quality and environmental conditions, which could potentially lead to incorrect subsequent classifications and misdiagnosis. Contemporary leukocyte detection methods exhibit limitations in dealing with images with fewer leukocyte features and the disparity in scale among different leukocytes, leading to unsatisfactory results in most instances. To address these issues, this paper proposes an innovative method of leukocyte detection: the Multi-level Feature Fusion and Deformable Self-attention DETR (MFDS-DETR). To tackle the issue of leukocyte scale disparity, we designed the High-level Screening-feature Fusion Pyramid (HS-FPN), enabling multi-level fusion. This model uses high-level features as weights to filter low-level feature information via a channel attention module and then merges the screened information with the high-level features, thus enhancing the model's feature expression capability. Further, we address the issue of leukocyte feature scarcity by incorporating a multi-scale deformable self-attention module in the encoder and using the self-attention and cross-deformable attention mechanisms in the decoder, which aids in the extraction of the global features of the leukocyte feature maps. The effectiveness, superiority, and generalizability of the proposed MFDS-DETR method are confirmed through comparisons with other cutting-edge leukocyte detection models using the private WBCDD, public LISC and BCCD datasets. Our source code and private WBCCD dataset are available at https://github.com/JustlfC03/MFDS-DETR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

IKAROS, encoded by IKZF1, is a tumor suppressor and a key hematopoietic transcription factor responsible for lymphoid and myeloid differentiation. IKZF1 mutations result in inborn errors of immunity presenting with increased susceptibility to infections, immune dysregulation, and malignancies. In particular, patients carrying IKZF1 gain-of-function (GOF) mutations mostly exhibit symptoms of immune dysregulation and polyclonal plasma cell proliferation. Herein, we describe seven new IKAROS GOF cases from two unrelated families, presenting with novel infectious, immune dysregulation and hematologic diseases. Two of the patients underwent allogeneic hematopoietic cell transplantation (HCT) due to poorly responsive complications. HCT was well-tolerated achieving full engraftment in both patients receiving reduced intensity, matched unrelated donor grafts, with no severe acute or chronic graft-vs-host-disease, and in remission from their diseases 2.5 and 4 years post-HCT, respectively. These results suggest that HCT is a valid and curative option in patients with IKAROS GOF disease and severe clinical manifestations., Competing Interests: Declaration of competing interest The authors have no conflicting financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Knees affected by haemophilic arthropathy exhibit distinct differences in both bone morphology and soft tissue behaviour. This study aims to analyse the morphological characteristics of the distal femur and patellofemoral joint in patients with haemophilia in comparison to normal healthy population., Material and Methods: Study was conducted as pair-matched case-control study with 43 individuals in both the haemophilia group and the control group. Patellar luxation, patellar tilt (PT), length of the patella in both axis (pAP, pML), depth and angle of trochlear sulcus (SD, SA), lateral trochlear inclination (LTI), medial and lateral femoral facet length (mFL, LFL), intercondylar depth (ID), transepicondylar axis (TEA) and lateral condyle length (LCL) were assessed on knee MRI. Correlation between Pettersson score and measured variables were also analysed., Results: PT was medial sided in 10 (23.2%) cases in haemophilic group. Mean values of pAP, pML, PT were significantly lower in haemophilia group (p < .001, p: .007, p = .001 respectively). There were no significant changes in SA (p = .628), SD (p = .340), LTI (p = .685), LFL (p = .241) and MFC-LFC (p = .770) whilst mFL was significantly longer in haemophilia group (p = .009). ID (p < .001), TEA (p = .007) and LCL (p = .001) were all shorter in haemophilia group. Pettersson score was inversely correlated with pAP, pML, ID, TEA, LCL, pML/SA and ID/LCL., Conclusion: Morphological changes in haemophilic arthropathy involve a smaller and medially-tilted patella, narrowed lateral condyle and transepicondylar axis, combined with reduced intercondylar depth. These alterations must keep in mind especially in pre- and intraoperative assessments for arthroplasty procedures., (© 2024 John Wiley & Sons Ltd.)

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency., Competing Interests: Declaration of competing interest K.M.M. reports consultancy fees from Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, CRISPR Therapeutics, Vifor Pharma, and Pharmacosmos; and research funding from Agios Pharmaceuticals and Pharmacosmos. M.D.C. reports consultancy fees from Novartis, Celgene/Bristol Myers Squibb, Vifor Pharma, and Ionis Pharmaceuticals; and research funding from Novartis, Celgene/Bristol Myers Squibb, La Jolla Pharmaceutical Company, Roche, Protagonist Therapeutics, and CRISPR Therapeutics. T.D.C. provides advisory support to Agios Pharma, Bristol Meyers Squibb, and Chiesi. K.H.M.K. reports consultancy fees from Agios Pharmaceuticals, Alexion Pharmaceuticals, Bristol Myers Squibb, Forma Therapeutics, Pfizer, NovoNordisk, and Vertex Pharmaceuticals; honoraria from Agios Pharmaceuticals and Bristol Myers Squibb; membership on an advisory committee for Bioverativ/Sanofi/Sangamo; and research funding from Agios Pharmaceuticals and Pfizer. H.A-S. reports consultancy fees from Novartis, Forma Therapeutics, Agios Pharmaceuticals, argenx, Moderna, Pharmacosmos, and Sobi; and research funding from Agios Pharmaceuticals, Amgen, Sobi, Novartis, and Vaderis Therapeutics. S.S. reports consultancy fees from Agios Pharmaceuticals, bluebird bio, Fulcrum Therapeutics, Chiesi, Celgene Corp (Bristol Myers Squibb), and Vertex; honoraria for CME activities from Plexus, CCO, and Physicians' Education Resource; advisory board travel from Agios Pharmaceuticals, Celgene Corp (Bristol Myers Squibb), and bluebird bio; research funding from Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, and Forma Therapeutics; and serving on a clinical trial steering committee for CRISPR/Vertex CTX001 for thalassemia. V.V. reports consultancy fees from Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, Novartis, Vifor Pharma, Pharmacosmos, IONIS Pharmaceuticals, Inc., and DisperSol Technologies, LLC; and research funding from Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, Novartis, Vifor Pharma, Pharmacosmos, IONIS Pharmaceuticals, Inc., DisperSol Technologies, LLC, and The Government Pharmaceutical Organization (GPO). A.T.T. reports consultancy fees from Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, Vifor Pharma, and Pharmacosmos; and research funding from Novartis, Celgene Corp (Bristol Myers Squibb), Agios Pharmaceuticals, Vifor Pharma, and Pharmacosmos., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Previous studies have demonstrated that various hematologic diseases (HDs) induce alterations in telomere length (TL). The aim of this study is to investigate whether genetically predicted changes in TL have an impact on the risk of developing HDs., Methods: GWAS data for TL and 11 HDs were extracted from the database. The R software package "TwoSampleMR" was employed to conduct a two-sample Mendelian randomization (MR) analysis, in order to estimate the influence of TL changes on the risk of developing the 11 HDs., Results: We examined the effect of TL changes on the risk of developing the 11 HDs. The IVW results revealed a significant causal association between genetically predicted longer TL and the risk of developing acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MANTLE), and hodgkin lymphoma (HODGKIN). However, there was no significant causal relationship observed between TL changes and the risk of developing chronic myeloid leukemia (CML), diffuse large b-cell lymphoma (DLBCL), marginal zone b-cell lymphoma (MARGINAL), follicular lymphoma (FOLLICULAR), monocytic leukemia (MONOCYTIC), and mature T/NK-cell lymphomas (TNK)., Conclusions: The MR analysis revealed a positive association between genetically predicted longer TL and an increased risk of developing ALL, AML, CLL, MANTLE, and HODGKIN. This study further supports the notion that cells with longer TL have greater proliferative and mutational potential, leading to an increased risk of certain HDs.

Background: Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki syndrome type 2 (KS2, MIM#300867), which accounts for only 5%-8% of KS. Previous studies suggested that female patients with KS2 may have a milder phenotype., Method: We summarized the phenotype and genotype of KS2 patients who were diagnosed in Shanghai Children's Medical Center since July 2017 and conducted a 1:3 matched case-control study according to age and sex to investigate sex-specific differences between patients with and without KS2., Results: There were 12 KS2 cases in this study, and 8 of them matched with 24 controls. The intelligence quotient (IQ) score of the case group was significantly lower than that of the control group (P < 0.001). In addition, both the incidence of intellectual disability (ID) (IQ < 70) and moderate-to-severe ID (IQ < 55) were significantly higher in the case group than those in the control group. No sex-specific difference was found in the incidence of ID or moderate-to-severe ID between the female cases and female controls, whereas there was a significant difference between male cases and male controls. Furthermore, the rate of moderate-to-severe ID and congenital heart disease (CHD) was significantly higher in the male group than that in the female group., Conclusions: Our results showed that a sex-specific difference was exhibited in the clinical phenotypes of KS2 patients. The incidence of CHD was higher in male patients, and mental retardation was significantly impaired. However, the female patients' phenotype was mild., (© 2024. The Author(s).)

Hematopoietic stem cell transplantation provides an effective cure for various hematological diseases, especially malignant hematological diseases, its treatment system has been continuously optimized, the source of donors has been expanding, the indications have been expanding, and the therapeutic effect has also made breakthroughs to a certain extent. At present, the status of hematopoietic stem cell transplantation technology in most hematological diseases is still unshakable, but the recurrence of the primary disease and complications related to hematopoietic stem cell transplantation are still two major clinical challenges that affect the long-term survival and quality of life of patients. Cell therapy represented by chimeric antigen receptor T (CAR-T) has made breakthrough progress in the treatment of refractory/recurrent B-cell malignancies. Compared with traditional drugs, cell therapy has unique in vivo metabolic characteristics, relying on immune specific recognition and the repair ability of stem cells. It is currently emerging in the treatment of blood tumors and the management of transplant complications. Multiple clinical studies have preliminarily demonstrated a new diagnostic and therapeutic model combining cell therapy with hematopoietic stem cell transplantation.

Background: Patients with leukemia rely on social and family support. This study aimed to explore the knowledge, attitude, and practice (KAP) toward leukemia among family members of patients with leukemia and the general population in southeast China., Methods: A cross-sectional study was conducted in September 2022 in southeast China (Anhui Province). The KAP scores and demographic data were assessed by questionnaire and analyzed by multivariable logistic regression and structural equation modeling., Results: A total of 760 valid questionnaires were collected, including 117 (15.39%) answered by family members of patients with leukemia. The mean knowledge (8.30 ± 2.79 vs. 8.72 ± 2.56, P = 0.103), attitude (52.17 ± 5.52 vs. 52.27 ± 5.53, P = 0.862), and practice (8.06 ± 2.00 vs. 8.18 ± 2.05, P = 0.547) scores were comparable among family members and the general population. Higher knowledge scores [OR = 1.18 (1.10, 1.27), P < 0.001] and higher attitude scores [OR = 1.05 (1.02, 1.09), P = 0.002] were independently associated with better practice scores. Being a family member of a patient with leukemia had no significant effect on the KAP scores., Conclusion: The participants demonstrated satisfactory knowledge, positive attitude, and appropriate practices toward leukemia, suggesting that access to information about leukemia to the general public might be sufficient in China. Health education might effectively improve knowledge, which could translate into improved attitude and practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin-3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

B vitamins improve animal performance through promote a wide range of metabolic pathways in animals as cofactors. Therefore, the impact of B-complex vitamin injection on performance, metabolic diseases, hematological parameters, and antioxidant status in pregnant Sannen goats and their newborn kids during the transition period was investigated. The pregnant goats (3 years old) were randomly divided into two groups: control (No B complex vitamins injection) and B complex vitamins (5 ml B complex vitamins injection per animal). B complex vitamins were injected twice intramuscularly into goats, according to the manufacturer's recommendation, during five- and three-weeks prior kidding. To determine the dry matter intake, feed samples were prepared. Also, metabolic diseases in goats and their offspring were recorded during the study. Blood samples of goats and newborn kids were taken seven days after parturition and measured for B vitamins concentrations, as well as hematological and antioxidant parameters. According to the results, the performance (body weight and dry matter intake) of goats and kids improved in B-complex vitamins group compared to the control group (P < 0.05). In addition, metabolic diseases were reduced in the goats and their offspring treated with B complex vitamins compared to the control group during the transition period (P < 0.05). The levels of cobalamin, pyridoxine, thiamine, folic acid, nicotinic, pantothenic, and unconjugated pteridine increased in the plasma of goats and their children by maternal B complex injection than in the control group during the transition period (P < 0.05). Higher (P < 0.05) levels of red blood cells, hemoglobin, hematocrit, total antioxidant status, glutathione peroxidase, superoxide dismutase, and catalase in goats' plasma, as well as red blood cells, hemoglobin, hematocrit, glutathione peroxidase, and superoxide dismutase in kids' plasma treated with B complex vitamins than the control group, were observed (P < 0.05). These results suggest that maternal Bcomplex vitamin injection is required for the improvement of performance, hematological status, and antioxidant status in pregnant goats and their kids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rituximab, anti-CD20 monoclonal antibody, has broad clinical application. The aim of this study is to compare the safety and cost of the original reference rituximab (MabThera) and its biosimilar (Riximyo). This retrospective analysis of 262 patients receiving Riximyo in the Department of Hematology of Wroclaw Medical University in Poland from the period of 1 October 2020 to 21 June 2021 focused on infusion-related reactions (IRRs), which occurred in 4,96% of patients ( N  = 13). 109 patients (41,6%) had previously been treated with the reference drug and 2 IRRs were reported after switching therapy. During the study period, after biosimilar introduction, the cost of rituximab decreased by 41%. Rixmyo while maintaining similar safety profile is much more cost-effective.

Gene modification of haematopoietic stem cells (HSCs) is a potentially curative approach to sickle cell disease (SCD) and offers hope for patients who are not eligible for allogeneic HSC transplantation. Current approaches require in vitro manipulation of healthy autologous HSC prior to their transplantation. However, the health and integrity of HSCs may be compromised by a variety of disease processes in SCD, and challenges have emerged in the clinical trials of gene therapy. There is also concern about increased susceptibility to haematological malignancies during long-term follow up of patients, and this raises questions about genomic stability in the stem cell compartment. In this review, we evaluate the evidence for HSC deficits in SCD and then discuss their potential causation. Finally, we suggest several questions which need to be addressed in order to progress with successful HSC manipulation for gene therapy in SCD., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier Ltd.)