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The editorial discusses the evolution of cellular immunotherapy, focusing on allogeneic hematopoietic stem cell transplantation and the development of more specific cellular immunotherapies to target pathogens and tumors. It highlights the challenges and successes of these therapies, including the use of genetically modified T cells and CAR-T cell therapy. The article emphasizes the need for careful quality control, regulatory compliance, and the high cost associated with personalized cellular therapies. Despite challenges, cellular therapies show promise in treating infections and various cancers, with ongoing research to optimize their efficacy and safety. [Extracted from the article]

Objectives: Procalcitonin (PCT) is a critical diagnostic biomarker for bacterial infections in patients. Numerous studies have shown that PCT have high sensitivity and specificity for diagnosing bloodstream infection. However, the cut-off value of PCT for the diagnosis of bloodstream infections in patients with hematolgic diseases is still unclear and unreliable. Methods: We conducted a retrospective study involving 2299 cases with hematological diseases and who had been performed blood culture and PCT test within 24 h. Results: For patients with hematological diseases, the serum PCT was slightly elevated in the BSI group. We found that most hematological patients with bloodstream infection were in the stage of severe neutropenia. The main infected strains were Escherichia coli (n = 84, 21%), Klebsiella pneumoniae (n = 61, 15.25%) and Pseudomonas aeruginosa (n = 65, 16.25%), and the increasing trend of PCT level was more obvious in patients infected with Gram-negative bacteria. ROC analysis results showed that the area under the receiver operating characteristic curve for distinguishing bacterial infection from non-bacterial infection was 0.554 (95%CI: 0.522–0.585) with the diagnostic threshold of BSI (PCT > 0.5ng/mL). Conclusions: In our study, low PCT levels were found in patients with hematological diseases, and a better cut-off value may be necessary to determine infection in hematology patients. [ABSTRACT FROM AUTHOR]

The article examines the increasing incidence of human parvovirus B19 infection in the U.S. and its impact on vulnerable groups such as pregnant women and children with sickle cell disease. Topics discussed include the rising cases of parvovirus infections, the complications observed in pregnant women, and the higher incidence of aplastic crises in children with sickle cell disease.

Given the lack of consensus on the screening and treatment for chronic rhinosinusitis (CRS) in the patients undergoing hematopoietic stem cell transplantation (HSCT), we reviewed the risk factors for CRS to improve the efficiency of sinonasal screening and analyzed the effect of treating CRS in search of guidance for modifying current management strategies for rhinosinusitis in HSCT patients. We conducted a nested case-control study in a retrospective cohort of hematologic patients receiving HSCT from April 2011 to April 2021 and collected data on demographics, smoking/atopic status, hematological diseases, and features of rhinosinusitis for analysis. The associated factors for control of rhinosinusitis and survival were analyzed. Fifty-eight CRS patients were identified, and another 116 age- and sex-matched controls were selected from HSCT patients without CRS. Allergy and smoking were risk factors for CRS in HSCT patients. The multivariable logistic analysis indicated that endoscopic sinus surgery (ESS) was an independent factor for better control of CRS. However, survival was not associated with rhinosinusitis-related factors, but only with hematologic-related factors, including allogenic HSCT, reduced-intensity conditioning, and remission. Sinonasal evaluation should be targeted to the high-risk group. ESS is effective in managing CRS, while control of CRS is not determinant of overall survival in patients receiving HSCT. [ABSTRACT FROM AUTHOR]

BACKGROUND Wide pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to kidney failure. PP naturally widens with age, but it is unclear whether the risks associated with greater PP are the same across all ages. METHODS We used Cox proportional hazards models to investigate the association of PP with (i) atherosclerotic cardiovascular disease (ASCVD) events or death and (ii) a 50% reduction in estimated glomerular filtration rate or kidney failure in the chronic renal insufficiency cohort (CRIC). We evaluated the association of time-updated PP with these outcomes, accounting for time-updated confounders using inverse probability weighting. RESULTS Among 5,621 participants with CKD, every 10-mmHg greater PP was associated with a 6% higher risk of an ASCVD event or death (hazard ratio [HR] = 1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite kidney outcome (HR = 1.17, 95% CI 1.16, 1.18). Greater PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21–61 years), but a higher risk of the composite kidney outcome in the oldest age tertile (71–79 years). While wide PP in participants that experienced the primary outcomes was predominantly driven by elevated SBP, PP remained significantly associated with the composite kidney outcome across all ages and with ASCVD events or death in the first age tertile when SBP was added to the Cox regression model. CONCLUSIONS Our findings suggest that the mechanism by which PP is associated with adverse outcomes may differ by age. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate and compare the risk of hematological adverse events (AEs) associated with CDK4/6 inhibitors using data from randomized controlled trials (RCTs) and Food and Drug Adverse Event Reporting System (FAERS) database. Methods: The PubMed, Embase, and Cochrane Library databases were searched for RCTs related to abemaciclib, palbociclib, and ribociclib. A network meta-analysis (NMA) was conducted to compare the risks of hematological AEs, and a disproportionality analysis was performed to detect signals of hematological AEs. Results: 16 RCTs comprising 16,350 breast cancer patients were included. Palbociclib and ribociclib had similar risks for hematological AEs, except a higher risk of grade 3–4 leukopenia observed with palbociclib (risk ratio [RR]: 7.84, 95% confidence interval [95%CI]: 1.33–41.28). Abemaciclib had a higher risk of anemia than both ribociclib (grade 1–4: RR: 2.23, 95% CI: 1.25 − 3.96; grade 3–4: RR: 3.52, 95% CI: 1.59 − 8.11) and palbociclib (grade 1–4: RR: 1.65, 95%CI: 1.03 − 2.59), but a lower risk of grade 3–4 of both leukopenia (RR: 0.12, 95%CI: 0.02 − 0.49) and neutropenia (RR: 0.15, 95%CI: 0.04 − 0.52) compared with palbociclib. Signals indicating occurrence of leukopenia, neutropenia, anemia, and thrombocytopenia were identified for three CDK4/6 inhibitors. Conclusion: Abemaciclib, palbociclib, and ribociclib showed significant but inconsistent hematological toxicity risks. [ABSTRACT FROM AUTHOR]

The risk of treatment‐related toxicities with programmed cell death 1 and its ligand (PD‐1/PD‐L1) inhibitors in patients with lung cancer is unclear and inconclusive. PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD‐1/PD‐L1 inhibitors versus placebo/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment‐related adverse events (TRAEs) or incidence and sample size. Random‐effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD‐1/PD‐L1 inhibitors significantly augmented the likelihood of developing all‐grade (RR, 1.03; 95% CI, 1.01–1.04, p <.01) and grade ≥3 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23, p <.01). PD‐1/PD‐L1 inhibitors substantially augmented the odds of developing treatment‐related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27–1.71, p <.01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11–1.82, p <.01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD‐1/PD‐L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD‐1/PD‐L1 inhibitors were significantly correlated with higher possibility of developing treatment‐related toxicities, especially SAEs and FAEs, compared with placebo/best supportive care controls. [ABSTRACT FROM AUTHOR]

Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo. In this work, by engineering vascular niche endothelial cells (VN-ECs), we generated functional HSPCs in vitro from ECs at various sites, including the aorta-gonad-mesonephros (AGM) region and the placenta. Firstly, we converted mouse embryonic HE cells from the AGM region (aHE) into induced HSPCs (iHSPCs), which have the abilities for multilineage differentiation and self-renewal. Mechanistically, we found that VN-ECs can promote the generation of iHSPCs via secretion of CX3CL1 and IL1A. Next, through VN-EC co-culture, we showed that placental HE (pHE) cells, a type of extra-embryonic HE cells, were successfully converted into iHSPCs (pHE-iHSPCs), which have multilineage differentiation capacity, but exhibit limited self-renewal ability. Furthermore, comparative transcriptome analysis of aHE-iHSPCs and pHE-iHSPCs showed that aHE-iHSPCs highly expressed HSC-specific and self-renewal-related genes. Moreover, experimental validation showed that retinoic acid (RA) treatment promoted the transformation of pHE cells into iHSPCs that have self-renewal ability. Collectively, our results suggested that pHE cells possess the potential to transform into self-renewing iHSPCs through RA treatment, which will facilitate the clinical application of placental endothelial cells in hematopoietic cell generation. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) constitutes a critical therapeutic approach for patients with malignant hematological disorders. Nevertheless, acute graft-versus-host disease (GVHD), one of the most prevalent complications associated with HSCT, remains a leading contributor to non-relapse mortality. In recent years, there has been an increasing focus on the interplay between chemokines and their receptors in the context of acute GVHD. Chemokines exert substantial effects across various pathological conditions, including autoimmune diseases, inflammatory processes, tumorigenesis, and metastatic dissemination. In this review, we aim to elucidate the role of chemokines in the pathogenesis of acute GVHD and further understand their potential as diagnostic biomarkers. We also present both preclinical and clinical insights into the application of chemokines in preventing and treating acute GVHD. The objective of this review is to offer novel perspectives on the clinical diagnosis and management strategies for acute GVHD. [ABSTRACT FROM AUTHOR]

Background: Blood pressure (BP) variability (BPV) and time in target range (TTR) are emerging vascular risk factors for dementia, independent of traditionally targeted mean BP. Objective: Determine whether BPV or TTR is most strongly associated with cognitive risk. Methods: In this post hoc analysis of the SPRINT trial, 8034 participants underwent repeated BP measurement and cognitive testing at baseline and follow-up. Visit-to-visit BPV was calculated as average real variability. TTR was the percent of time in desired treatment arm target range (standard: 120–140 mmHg systolic BP; intensive: 110–130 mmHg systolic BP). Adjudicated clinical outcomes were no cognitive impairment, mild cognitive impairment (MCI), and probable dementia. We investigated a direct comparison of BPV and TTR in predicting cognitive risk, stratified by BP treatment group. Results: Elevated BPV was associated with increased risk for MCI (adjusted HR: 1.21 [95% CI 1.10, 1.33], p < 0.001) and MCI/dementia (HR: 1.17 [95% CI 1.07, 1.27], p < 0.001) in the standard group, and dementia (HR: 1.17 [95% CI 1.01, 1.36], p = 0.039) in the intensive group. Higher TTR was related to lower dementia risk (HR: 0.72 [95% CI 0.60, 0.86], p < 0.001) in the intensive group only. Conclusions: Visit-to-visit BPV outperformed TTR in predicting risk for MCI and MCI/dementia. TTR was more strongly associated with dementia risk under intensive treatment. Findings were independent of mean BP in a cohort with rigorously controlled BP and suggest newer aspects of BP control may be harnessed to further reduce cognitive risk. Clinical trial information: ClinicalTrials.gov; NCT01206062. [ABSTRACT FROM AUTHOR]

Background: Black adults have higher dementia risk than White adults. Whether tighter population-level blood pressure (BP) control reduces this disparity is unknown. Objective: Estimate the impact of optimal BP treatment intensity on racial disparities in dementia. Methods: A microsimulation study of US adults ≥18 across a life-time policy-planning horizon. BP treatment strategies were the Systolic Blood Pressure Intervention Trial (SPRINT) protocol, the Eighth Joint National Committee (JNC-8) recommendations, and usual care (non-intervention control). Outcomes were all-cause dementia, atherosclerotic cardiovascular disease (ASCVD), stroke, myocardial infarction, non-ASCVD death, global cognitive performance, and optimal brain health (being free of dementia, cognitive impairment, or stroke). Population-level and individual-level effects stratified by race were estimated. Results: Optimal population-level implementation of a SPRINT-based BP treatment strategy, compared to usual care, would increase average annual dementia incidence in White, but not Black, adults (1% versus 0%), due to hypertensive individuals' greater survival, and reduce annual ASCVD events more in Black than White adults (13% versus 5%). Under a SPRINT-based strategy, individuals with hypertension gained more years lived without dementia, ASCVD, myocardial infarction, or stroke and more years lived in optimal brain health. A SPRINT-based strategy did not attenuate individual-level race disparities in outcomes, except stroke. Due to longer life expectancy, a SPRINT-based strategy did not substantially reduce lifetime dementia risk in either group. The JNC-8-based strategy had similar but smaller effects as the SPRINT-based strategy. Conclusions: Our results suggest that tighter population-level BP control would not reduce population-level disparities in dementia between US Black and White adults. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess clinical decision-making associated with the use of a multi-analyte blood biomarker (BBM) test among patients presenting with signs or symptoms of mild cognitive impairment or dementia. Methods: The Quality Improvement PrecivityAD2 (QUIP II) Clinician Survey (NCT06025877) study evaluated the clinical utility of the PrecivityAD2™ blood test in a prospective, single cohort of 203 patients presenting with symptoms of Alzheimer's disease (AD) or other causes of cognitive decline across 12 memory specialists. The PrecivityAD2 blood test (C2N Diagnostics, St. Louis, MO) combines the plasma Aβ42/Aβ40 ratio and the p-tau217/np-tau217 ratio (%p-tau217) measurements in a statistical algorithm to yield an Amyloid Probability Score 2 (APS2) that informs on the likelihood of brain amyloid plaques. After receiving the BBM test results, clinicians completed surveys on management strategies for each patient. Results: Patients had a median age of 74, 53% were female, and 28% were traditionally under-represented in Black, Hispanic, and Asian groups. The composite primary endpoint, defined as a change in AD diagnostic certainty, drug therapy, or additional brain amyloid evaluation pre- and post-BBM testing, was 75% (p < 0.0001 versus the pre-specified threshold of 20% clinically meaningful change). Anti-AD medication orders decreased among negative APS2 patients and increased among positive APS2 patients (p < 0.0001). Additional brain amyloid testing decreased among negative APS2 patients (p < 0.0001). Conclusions: This blood biomarker test can help memory specialists guide patients to anti-AD therapies as well as rule out AD to allow for other diagnostic considerations. [ABSTRACT FROM AUTHOR]

Objective Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality. Current expanded treatment recommendations result in the inclusion of a large percentage of the obstetric population, which has limited their adoption. The purpose of this study was to identify a population at high risk for VTE, with minimal impact on the number of patients that would qualify for expanded treatment. Study Design We performed a retrospective analysis of a large obstetric population. International Classification of Diseases, 10th Revsion (ICD-10) codes for VTE were used to identify patients presenting for obstetric or postpartum (PP) care from January 2016 to March 2018. The review focused on high-risk factors (history of VTE or high-risk thrombophilia), antepartum hospital admissions that were >72 hours in the previous 30 days, use of sequential compression devices, body mass index (BMI; kg/m 2), age, and mode of delivery. Pharmacologic treatment efficacy was set at 90, 75, or 50%. Results During the 27-month review period, there were 120,235 deliveries and 93 had a VTE event in the index pregnancy or within 4 weeks PP (7.7/10,000 births). A history of VTE or high-risk thrombophilia was seen in 25.8% of cases. Antepartum admission was noted in 40.9%, and the combination of cesarean delivery (CD) with age and BMI ≥35 (Age + BMI + CD) was noted in 17.3% of PP cases. Targeting these latter two groups for VTE prophylaxis with a 75% efficacy suggests that 34% of the VTE events would likely have been prevented while increasing the total population treated by approximately 2%. Conclusion Expanding pharmacologic prophylactical coverage to include an antepartum admission of >72 hours and those with Age + BMI + CD would result in about a one-third reduction in total VTE events with about 2% requiring treatment. These data support some of the suggested recommendations for expanded pharmacological deep venous thrombosis prophylaxis. Key Points CD, and BMI and age >35 are high-risk factors for VTE. Antepartum admission >72 hours is a high-risk factor for VTE. Targeting antepartum admissions, CD, and BMI and age >35 would reduce VTE events by about 33%. [ABSTRACT FROM AUTHOR]

Background: It is known that viral infections are associated with increased morbidity and mortality in immunocompromised children. Few reports describe the clinical manifestations and outcomes of COVID-19 infection in children and adolescents with benign and malignant hematological disease with a large sample size from our Egyptian population. Aim: As a preliminary step in developing a national registry for children and adolescents with hemato-oncological disease who were diagnosed with COVID-19 infection, in this study we aimed to determine (a) the frequency of COVID-19 infection in children with hematological disease, (b) the presenting clinical manifestations, and (c) the associated underlying disease outcome and its clinical determinants. Methods: We collected data from medical records of a retrospective cohort including all children and adolescent patients who were known to have a benign or malignant hematological disease attending the hematology and oncology outpatient clinic or were hospitalized between February 2022 and March 2023 in a university hospital in Cairo, Egypt, for tertiary care. All patients (n = 620) were tested for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test by nasopharyngeal swab. For all patients, the collected data included the demographic data, diagnosis, cause of hospital visit, cause and duration of admission if needed, presence of symptoms suggestive of COVID-19 infection, and concurrent medications. Baseline laboratory investigation were collected included complete blood count (CBC), liver and kidney functions, C-reactive protein (CRP), serum ferritin, lactate dehydrogenase, and coagulation test. For COVID-19-positive patients, the additional data collected included the duration of COVID-19 infection, its course, full examination during this illness, its severity, and the outcome of COVID-19 infection and the underlying disease. Results: Out of the 620 children and adolescents with benign (n = 271) and malignant (n = 349) hematological diseases in in-patients and out-patients' settings, 86 patients (13.8%) tested positive for SARS-CoV-2. COVID-19 infection was more common in patients with hematological malignancy (n = 56, 65.1%) than those with benign hematological disease (27 patients, 31.4%). Among COVID-19-positive patients, 20 patients (23.3%) required intensive care unit admission compared to 30 (5.6%) COVID-19-negative patients (p-value < 0.000). Death was reported in 5 COVID-19-positive patients (5.8%) compared to 19 in COVID-19-negative patients (3.6%) (p-value = 0.314). The factors associated with mortality in COVID-19-positive patients (3 patients with hematological malignancy and 2 patients with aplastic anemia) was abnormal neurological examination [OR = 17.3; p-value = 0.009]. Conclusion: The current study showed that COVID-19 was higher among patients with hematological malignancies than those with benign hematological disease. COVID-19 was tolerable among the studied patients with underlying hematological disease where 94.1% of the COVID-19-positive patients survived. Mortality was associated with abnormal neurological examination in COVID-19-positive patients with underlying hematological disease. [ABSTRACT FROM AUTHOR]

Objectives: Vitamin B12 (Cobalamin or Cbl) plays a crucial role in normal human growth and development, as well as in neurological, cardiovascular, and immune systems. Previous studies reported association of high levels of cobalamin with solid cancers, hematological disorders, and liver diseases. Reporting the frequency of comorbid diseases with high serum Vitamin B12 level in patients attending KSAMC at Madinah. Methods: This is a retrospective, cross-sectional study on data collected during 1 year (May 2022–May 2023) from 3511 report, patients with high cobalamin blood level (normal upper limit 771 pg/mL) as determined in our laboratory on COBAS® were included. Patient’s clinical diagnosis, medication history and other laboratory parameters performed were also checked for disease comorbidities. Results: Our results revealed statistically significant increase in serum Vitamin B12 in patients with diabetes mellitus, with the use of this vitamin as supplement therapy 53.2% (the predominant comorbidity), together with liver, blood, chest, kidney, thyroid and neurological diseases, and various solid tumors. A positive correlation was found between serum Vitamin B12, age and laboratory parameters including aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin, and a negative correlation was seen between serum Vitamin B12 level, serum albumin (ALB), red blood cell count, hemoglobin, and free T3 (FT3). While, no significant correlation with the rest of the checked parameters was detected. Conclusion: This study found high serum level of Vitamin B12 associated with various disease entities, for example, (diabetes mellitus treated with Vitamin B12 as supplement therapy, liver, blood, chest, kidney, thyroid, neurological diseases, and various solid tumors), so when Vitamin B12 is high, further investigations will be recommended. Most of the comorbidities were benign in Saudis, followed by Egyptians with predominance of female-aged 50–70 year old. [ABSTRACT FROM AUTHOR]

The use of nanotechnology to make nanoformulations/nanocarriers is a rapidly evolving field of study with the potential to fundamentally improve the treatment outcomes for diverse disease states. The use of nanoformulations allows for targeted drug delivery to diseased sites and reduced unwanted side effects. There have been many FDA-approved nanoformulations for the treatment of complex disease states such as advanced non‐small cell lung cancer, secondary metastatic breast cancer, primary metastatic pancreatic cancer, Kaposi's sarcoma related to AIDS, ovarian cancer, multiple myeloma, leukemia, amyloidosis, and age-related macular degeneration. While most nanoformulations are approved for cancer therapy, FDA-approved nanoformulations are effectively employed to treat autoimmune disorders, metabolic disorders, ophthalmic conditions, neurological diseases, hematological disorders, and inflammatory diseases. Further, novel nanoformulations are in various phases of clinical development for endocrine disorders, complex cancers, skin, ocular, blood, nervous system, cardiovascular, immune, and inflammatory disorders. [ABSTRACT FROM AUTHOR]

The risk of fungal, bacterial, and viral infections is higher in children with hematological and solid malignancies, particularly during periods of profound neutropenia. Although early administration of antimicrobial agents is common, optimizing pharmacological therapy in pediatric patients with cancer is challenging because of their variable pharmacokinetics compared with adults, including differences in body mass and augmented renal clearance, as well as chemotherapy-induced organ toxicity. Therapeutic drug monitoring, which involves measuring drug concentrations in serum or plasma at specific timepoints and adjusting doses accordingly, can be applied to various medications. While standardized targets for all antimicrobial agents in children are lacking, therapeutic drug monitoring appears to be beneficial in preventing serious toxicity and addressing treatment failure or non-compliance. This narrative review aims to analyze current perspectives on therapeutic drug monitoring for antimicrobial drugs in the special population of children with hematological or oncological diseases, including those undergoing hematopoietic cell transplantation. The review provides evidence on the clinical benefits of this method and explores potential future developments in this area. [ABSTRACT FROM AUTHOR]

Despite the advances of CAR-T cells in certain hematological malignancies, mostly from B-cell derivations such as non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, a significant portion of other hematological and non-hematological pathologies can benefit from this innovative treatment, as the results of clinical studies are demonstrating. The clinical application of CAR-T in the setting of acute T-lymphoid leukemia, acute myeloid leukemia, solid tumors, autoimmune diseases and infections has encountered limitations that are different from those of hematological B-cell diseases. To overcome these restrictions, strategies based on different molecular engineering platforms have been devised and will be illustrated below. The aim of this manuscript is to provide an overview of the CAR-T application in pathologies other than those currently treated, highlighting both the limits and results obtained with these settings. [ABSTRACT FROM AUTHOR]

Simple Summary: The transcriptional regulation of BCL11A shows stage-specific characteristics and plays an important role in the development of hematopoietic lineages, which is closely related to the occurrence of blood cell diseases. We aim to summarize the functions of BCL11A within the hematopoietic system and related diseases and discuss its feasibility as a therapeutic target for the treatment of hematological disorders. B-cell lymphoma/leukemia 11A (BCL11A) is a crucial transcriptional regulator, widely recognized for its role in controlling fetal hemoglobin and its potential as a gene therapy target for inherited hemoglobinopathies. Beyond this, recent studies have also highlighted its key role in the maturation and function of immune cells and erythrocytes, mediated through the regulation of various molecules during hematopoietic development. The dysregulation of BCL11A disrupts downstream molecular pathways, contributing to the development of several hematological malignancies, particularly leukemias. This review provides a comprehensive overview of the role of BCL11A in normal and malignant hematopoiesis, details the hematological disorders associated with its dysregulation and explores the current therapeutic strategies targeting this transcription factor. [ABSTRACT FROM AUTHOR]

The document discusses a rare case of primary myelofibrosis (PMF) leading to pulmonary alveolar proteinosis (PAP) in a 41-year-old woman. The patient's symptoms included cough, shortness of breath, and splenomegaly, with a diagnosis confirmed through imaging, laboratory tests, and bone marrow analysis. Treatment involved ruxolitinib, radiotherapy, and ultimately allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in the resolution of both PMF and PAP. The successful outcome highlights the potential of allo-HSCT in managing complex cases like this. [Extracted from the article]

Utilizing RBC or PLT-related parameters to establish rules for the PLT-O reflex test can assist laboratories in quickly identifying specimens with interfered PLT-I that require PLT-O retesting. Prospective PLT-I and PLT-O testing was performed on 6857 EDTA-anticoagulated whole blood samples, split randomly into training and validation cohorts at a 2:3 ratio. Reflex and non-reflex groups were distinguished based on the differences between PLT-I and PLT-O results. By comparing RBC and PLT parameter differences and flags in the training set, we pinpointed factors linked to PLT-O reflex testing. Utilizing Lasso regression, then refining through univariate and multivariate logistic regression, candidate parameters were selected. A predictive nomogram was constructed from these parameters and subsequently validated using the validation set. ROC curves were also plotted. Significant differences were observed between the reflex and non-reflex groups for 19 parameters including RBC, MCV, MCH, MCHC, RDW-CV, RDW-SD, Micro-RBC#, Micro-RBC%, Macro-RBC#, Macro-RBC%, MPV, PCT, P-LCC, P-LCR, PLR,"PLT clumps?" flag, "PLT abnormal histogram" flag, "IDA Anemia?" flag, and "RBC abnormal histogram" flag. After further analysis, Micro-RBC#, Macro-RBC%,"PLT clumps?", and "PLT abnormal histogram" flag were identified as candidate parameters to develop a nomogram with an AUC of 0.636 (95 %CI: 0.622–0.650), sensitivity of 42.9 % (95 %CI: 37.8–48.1 %), and specificity of 90.5 % (95 %C1: 89.6–91.3 %). The established rules may help laboratories improve efficiency and increase accuracy in determining platelet counts as a supplement to ICSH41 guidelines. [ABSTRACT FROM AUTHOR]

Background: Unexplained recurrent miscarriage (RM) is still an unsolved reproductive health problem. Inherited thrombophilias have been one of the causes. Mutation in genes encoding coagulation proteins, including prothrombin (PT G20210A) and methylenetetrahydrofolate reductase (MTHFR) genes, increase tendency for venous thromboembolism. This study aimed to evaluate association between polymorphisms in prothrombine and MTHFR genes with RM. We also evaluated association between protein C (PC), protein S (PS), antithrombin III (ATIII), and homocystiene with RM. Materials and Methods: We conducted a case-control study on women with history of miscarriages and healthy controls. Genetic analysis was done using (TaqMan) polymerase chain reaction (PCR) technique and the other tests were performed to check general health indications and thrombophilia markers. Results: In this study, 195 RM group (group I) participants and 90 healthy controls (group II), PC, PS, ATIII deficiency and Hyperhomocysteinemia were in 7.2, 65.6, 9.2, 10.8% of group I respectively, but was 1.1, 7.8, 2.2, 2.2% of group II. PT G20210A showed two in group I were A/G, no A/G in group II, and no AA carrier in the either group. G allele was observed in 99.5% of the group I and 100% of the group II, while A allele was detected in 0.5% of group I. MTHFR C677T gene showed C/T mutation in 33.3% of group I and 32.2% of group II, while T/T mutation was detected in 12.8% of group I and 8.9% of the group II. C allele was found in 70.5% of group I and 75% of group II, while T allele was found in 29.5% of group I and 25% of group II (P=0.269). Conclusion: PT G20210A and MTHFR C677T gene mutations are not correlated with RM in the Egyptian population. However, Egyptian women with RM are strongly associated with hyperhomocysteinemia, PC, PS, and ATIII deficiencies (registration number: NCT03209063). [ABSTRACT FROM AUTHOR]

The article in the Journal of Cutaneous Pathology discusses a case of Acantholytic PRIDE syndrome in a 63-year-old male with chronic myeloid leukemia who developed pus-filled lesions on his limbs after starting imatinib therapy. The patient was treated with topical clobetasol ointment, levocetirizine tablets, and moisturizers, showing improvement at a 3-month follow-up. The syndrome is linked to tyrosine kinase inhibitors like EGFRIs and presents with various cutaneous manifestations, requiring differentiation from other conditions like Grover disease and AGEP. The study highlights the need for further research to understand the exact mechanisms behind acantholysis in PRIDE syndrome. [Extracted from the article]

Clonal hematopoiesis (CH) is a condition in which hematopoietic stem cells (HSCs) acquire mutations seen in leukemia. While individuals with CH generally do not show signs of hematologic disease, the condition becomes more common with age and correlates with age-related diseases, especially cardiovascular disease (CVD). JAK2 mutations in HSCs can lead to CH and correlate with atherosclerosis, but the condition has been difficult to study because of challenges modeling the mutant cells at very low frequency. In this issue of the JCI, Liu et al. developed a low-allele-burden (LAB) mouse model in which a small number of bone marrow cells carrying the Jak2VF mutation were transplanted into mice predisposed to hyperlipidemia. Along with recapitulating features of plaque development, the authors identified the phagocytic receptors MERTK and TREM2 in WT cells as downstream of the inflammatory cytokine IL-1. These findings provide potential targets for preventing or treating patients at risk for CH-associated CVD. [ABSTRACT FROM AUTHOR]

Background and Objectives: Lower respiratory tract infections are particularly frequent in hematological patients; their early diagnosis and the timely start of targeted therapy are essential. Bronchoalveolar lavage (BAL) can provide a microbiological sample from the lower airways in a minimally invasive way. This study aimed to determine the diagnostic yield of BAL in hematological patients for microbiological purposes and its influence on modifying the therapeutic strategy. Material and Methods: This multicenter, retrospective, observational study included data from 193 consecutive patients from two centers from January 2020 to October 2022. The patients underwent a bronchoscopy with BAL in cases of pulmonary infiltrates suspicious of pulmonary infection. The demographic data, presenting symptoms, level of immunosuppression, chest CT changes, BAL sampling results, and antimicrobiological drug administration were analyzed. Results: Of the 193 procedures, 143 (74.1%) were performed on hospitalized patients, while 50 were performed on outpatients. In 53.9% of the cases, the BAL isolated at least one germ; in particular, if the procedure was carried out within 72 h of presenting symptoms, the probability of isolating the germ increased significantly (74.3%, p = 0.04). Among the isolated germs, 59.4% were viruses, 28.6% were bacteria, and 12% were fungi. The patients with higher immunosuppression and the febrile ones underwent BAL earlier than the patients with mild immunosuppression (p = 0.01) and those with other presenting symptoms (p = 0.0001). BAL positivity led to a change in empirical antimicrobial therapy in 79 out of 104 cases (77% vs. 36.3%; p < 0.001); these data were also confirmed among the hospitalized patients (81% vs. 44%; p < 0.001). The isolation of a pathogen through BAL and the degree of patient immunosuppression negatively influenced patient survival (p < 0.05 and p < 0.01, respectively). Conclusions: BAL is confirmed as a valid approach for evaluating pulmonary infiltrates in hematological patients, given the excellent clinical impact and high diagnostic yield, mainly if performed early after symptom presentation. However, ongoing antimicrobial treatments at the time of BAL may have potentially affected the diagnostic yield of the procedure. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with various hematological disorders. Understanding the pathology of erythrocytes (red blood cells) in coronavirus infection may provide insights into disease severity and progression. Objective: To review and analyze the general pathology of erythrocytes in patients infected with SARS-CoV-2, focusing on clinical and laboratory findings across different severity groups. Methods: Patients were classified into four groups based on clinical criteria: Group 1: Regular group (fever, respiratory symptoms, and radiographic evidence of pneumonia). Group 2: Severe group (shortness of breath >30 breaths/min, peripheral blood oxygen saturation <92% at rest, extensive pneumonia, respiratory failure requiring mechanical ventilation, and/or organ failure necessitating intensive care). Group 3: Low saturation group (peripheral blood oxygen saturation <85% at rest). Group 4: Erythroblastosis group (erythroblast count >0.5% among total nucleated blood cells). Clinical laboratory investigations included major routine studies and scanning microspectrophotometry to measure hemoglobin (Hb) spectra in unstained erythrocytes. Results: Erythroblasts were detected in approximately 30% of SARS-CoV-2 patients, predominantly in the severe group. Serum ferritin, C-reactive protein (CRP), and anisocytosis were strongly correlated with disease severity. Microspectrophotometric studies revealed significant changes in hemoglobin adsorption spectra, with an increase in Hb absorbance at 420 nm in severe cases compared to normal controls. Conclusions: Elevated serum ferritin, CRP levels, anisocytosis, and altered hemoglobin absorption at 420 nm wavelength are associated with adverse outcomes in SARS-CoV-2 infection. These findings highlight the potential utility of hematological parameters as markers for disease severity and prognosis in viral infections. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease. Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data. We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol. The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure. However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is a complex reparative process in response to chronic liver injuries, with limited effective therapeutic options available in clinical practice. During liver fibrosis, liver sinusoidal endothelial cells (LSECs) undergo phenotypic changes and also play a role in modulating cellular communications. Si-Wu-Tang (SWT), a traditional Chinese herbal remedy, has been extensively studied for its effectiveness in treating hematological, gynecological and hepatic diseases. Materials and methods: The component of SWT were identified by ultra-high-performance liquid chromatography (UHPLC). After establishing bile duct ligation (BDL)-induced liver fibrosis mice model and VEGFA-stimulated LSEC model, we invested the mechanism of SWT through RNA sequencing combined with molecular biology techniques. Results: SWT significantly improved the sinusoidal permeability and liver fibrosis induced by BDL and effectively regulated pathological processes in LSECs, such as angiogenesis, cell adhesion, basement membrane formation and defenestration. The anti-fibrosis effects of SWT were attributed to the inhibition on LSEC adhesion via COL8A1, on LSEC angiogenesis via IL-1β and the induction of LSEC defenestration by OLR1. Additionally, SWT disrupted the intercellular crosstalk between LSECs and hepatic stellate cells (HSCs) driven by IL-1β, thus alleviating liver fibrosis. Conclusion: SWT collectively ameliorated liver fibrosis by inhibiting the COL8A1/IL-1β/OLR1 pathways associated with LSEC angiogenesis, adhesion and defenestration, as well as suppressing LSEC secretion of IL-1β to reduce HSC activation. [ABSTRACT FROM AUTHOR]

Objective: To understand the prevalence and associated risk factors of lower extremity arterial disease (LEAD) in Chinese diabetic patients and to construct a risk prediction model. Methods: Data from the Diabetes Complications Warning Dataset of the China National Population Health Science Data Center were used. Logistic regression analysis was employed to identify related factors, and machine learning algorithms were used to construct the risk prediction model. Results: The study population consisted of 3,000 patients, with 476 (15.9%) having LEAD. Multivariate regression analysis indicated that male gender, atherosclerosis, carotid artery stenosis, fatty liver, hematologic diseases, endocrine disorders, and elevated glycosylated serum proteins were independent risk factors for LEAD. The risk prediction models constructed using Logistic regression and MLP algorithms achieved moderate discrimination performance, with AUCs of 0.73 and 0.72, respectively. Conclusion: Our study identified the risk factors for LEAD in Chinese diabetic patients, and the constructed risk prediction model can aid in the diagnosis of LEAD. [ABSTRACT FROM AUTHOR]

Sickle cell anemia (SCA) is a monogenic blood disease with complex and multifactorial pathophysiology. The endocannabinoid system (ECS) could be a candidate for modulating SCA complications, such as priapism, as it has demonstrated an essential role in hematopoiesis, platelet aggregation, and immune responses. We evaluated the association of ECS-related single nucleotide polymorphisms (SNP) (FAAH rs324420, MAGL rs604300, CNR1 rs7766029, and CNR2 rs35761398) with priapism in a Brazilian SCA cohort. The study involved 138 SCA patients (n = 80 with priapism and n = 58 without priapism). SCA was detected with HPLC, and the Hb SS genotype was confirmed with PCR-RE. Alpha thalassemia mutations were detected with Multiplex-PCR, and SNP genotyping was performed using TaqMan genotyping assays. We observed a lower frequency of -α3.7kb-thalassemia mutation in patients with priapism than in patients without this complication (p < 0.001), and in adjusted multivariate analyses TT-CC genotype of CNR2 rs35761398 was associated with a lower chance of developing priapism (OR = 0.386 [0.175–0.854], p = 0.019) and a lower risk of it over time (HR = 0.634 [0.402–0.987], p = 0.049). The SCA ischemic priapism is related to unbalanced vasodilation/vasoconstriction pathways, such as decreased RhoA/Rho-kinase (ROCK) signaling. Since activating the type 2 cannabinoid receptor (CB2) decreases RhoA activation, we suggest a novel approach to SCA priapism involving CB2. [ABSTRACT FROM AUTHOR]

Background: The tolerance and dynamic regulation of the maternal immune system during pregnancy are pivotal for ensuring fetal health. Immune cell subsets play a complex and crucial role in this process, closely linked to the neonatal health status. Despite recognizing the significance of dysregulation in the quantity and activity of immune cells in neonatal disease occurrence, their specific roles remain elusive, resulting in a dearth of clinically viable interventions for immune‐mediated neonatal diseases. Materials and Methods: Employing two‐sample Mendelian randomization (MR) methodology, this study systematically investigated 446 leukocyte features (N = 500,675), including leukocyte subsets, absolute cell (AC) counts, and morphological parameters (MP) and their correlation with seven adverse fetal outcomes (N = 1,100,458), encompassing fetal growth restriction (FGR), preterm birth (PTB), neonatal jaundice (NNJ), digestive system disorders of fetus and newborn (DSDFN), hemorrhagic and hematological disorders of fetus and newborn (HDFN), respiratory distress of newborn (RDN), and transitory disorders of metabolism specific to fetus and newborn (TDMSFN). Results: The results unveiled significant causal relationships between 301 leukocyte subsets and these seven adverse fetal outcomes, with 259, 245, 15, 44, 11, 32, and 68 pairs of notable associations for each adverse outcome, respectively. Furthermore, the study highlighted potential pathogenic mechanisms underlying the mutual influence among neonatal diseases. MR results indicated FGR as a robustly correlated risk factor for PTB and NNJ and showed a reciprocal causal relationship between NNJ and FGR. PTB exhibited a positive correlation with HDFN. Conclusions: This study provided profound insights into the intricate regulatory mechanisms of leukocyte subsets in neonatal diseases, paving the way for new avenues in the diagnosis and treatment of associated disorders. [ABSTRACT FROM AUTHOR]

The realm of hematopoietic stem cell transplantation (HSCT) has witnessed remarkable advancements in elevating the cure and survival rates for patients with both malignant and non-malignant hematologic diseases. Nevertheless, a considerable number of patients continue to face challenges, including transplant-related complications, infection, graft failure, and mortality. Inflammasomes, the multi-protein complexes of the innate immune system, respond to various danger signals by releasing inflammatory cytokines and even mediating cell death. While moderate activation of inflammasomes is essential for immune defense and homeostasis maintenance, excessive activation precipitates inflammatory damage. The intricate interplay between HSCT and inflammasomes arises from their pivotal roles in immune responses and inflammation. This review examines the molecular architecture and composition of various types of inflammasomes, highlighting their activation and effector mechanisms within the context of the HSCT process and its associated complications. Additionally, we summarize the therapeutic implications of targeting inflammasomes and related factors in HSCT. [ABSTRACT FROM AUTHOR]

Background: Among the Alzheimer's disease (AD) biomarkers measured in blood, phosphorylated forms of tau (p-tau) have been shown to exhibit a particularly high diagnostic potential. Here, we performed a comprehensive method comparison study, followed by evaluation of the diagnostic performance of eight recent plasma p-tau immunoassays targeting different tau phosphorylation sites, different tau fragments, and that are measured by two distinct platforms. Methods: We enrolled a cohort of 40 patients with AD at the stage of dementia (AD-dem) characterized by positive CSF A + T + profile, and a control group of 40 cognitively healthy participants (Control), to conduct a comprehensive method comparison for three plasma p-tau181 and five plasma p-tau217 assays run on the Simoa® HD-X™ or Lumipulse® G600II/G1200 platforms. Design of the compared assays differed in regard to: (1) tau phosphorylation site targeted by the capture antibody (T181 or T217), and (2) epitope of the pan-tau detector antibody (N-terminal or mid-region). For each of the assays we determined precision and analytical sensitivity parameters and used Passing-Bablok regression and Bland-Altman plots for pairwise comparison of p-tau181 or p-tau217 assays. Subsequently, we evaluated the diagnostic accuracy of all the assays for discrimination between AD-dem and Control groups. Results: We found a strong, positive correlation between all the measurements. Fixed and/or proportional bias was observed for each of compared p-tau181 assay pairs or p-tau217 assay pairs. While both plasma p-tau181 and p-tau217 levels were significantly increased in AD-dem vs. Control groups as measured by all assays, higher median concentration AD-dem/Control fold change and AUC values were observed for p-tau217 (assays range: fold change 3.72–6.74, AUC 0.916–0.956) compared with p-tau181 (assays range 1.81–2.94, AUC 0.829–0.909), independently of the platform used. No significant differences were observed between diagnostic performance of p-tau181 assays or p-tau217 assays targeting tau N-terminus or mid-region. Conclusions: Although all plasma p-tau measurements enabled discrimination between clinical groups, p-tau217 assays showed the highest robustness, independently of the pan-tau detector antibody targeting N-terminal or mid-region, and independently of the platform used. Considering the observed method disagreement in measured absolute concentrations, we stress the need for development of certified reference material, harmonizing measurements across different platforms. [ABSTRACT FROM AUTHOR]

Background: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications. Methods: Here, we conducted a retrospective study involving 90 pediatric patients with hematological disorders who underwent haplo-HSCT at a single center. All patients were subjected to MMF-related SNP testing, combined with common clinical characteristics, to be correlated with post-transplant complications. Results: We observed that all 15 MMF-related SNPs were in Hardy-Weinberg equilibrium. Based on multivariate Cox regression analysis of post-transplant complications, we discovered that SLCO1B1 (521T > C) variant genotype was an independent protective factor for chronic GvHD (HR = 0.25, 95% confidence interval (CI) (0.08–0.84)). For viral infection, CYP2C8 (1291 + 106T > C) variant genotype was an independent risk factor for cytomegalovirus infection (HR = 2.98, 95% CI (1.18–7.53)). As to hemorrhagic cystitis, SLCO1B1 (1865 + 4846T > C) variant genotype was an independent protective factor, while older age was considered as an independent risk factor (HR = 0.41, 95% CI (0.19–0.85); HR = 2.52, 95% CI (1.14–5.54), respectively). No statistical significance was discovered between common clinical characteristics and MMF-related SNPs with other complications, including grade II-IV/III-IV acute GvHD, Epstein-Barr virus infection, peri-engraftment syndrome, and capillary leak syndrome. We also discovered SLCO1B1 (597 C > T) and SLC29A1 (-162 + 228 A > C) variant genotypes are both independent factors for cumulative incidence of relapse after haplo-HSCT (HR = 4.02, 95% CI (1.42–11.44); HR = 0.18, 95% CI (0.07–0.43), respectively). Conclusions: Our findings highlight the significance of MMF-related transporters and metabolic enzymes SNPs in the development of post-transplant complications, contributing to facilitating personalized risk assessment and improving the clinical management in haplo-HSCT patients. [ABSTRACT FROM AUTHOR]

Inhibiting the PD-1/PD-L1 pathway using immunomodulators has demonstrated promising outcomes in clinics. Immunomodulators can effectively target immune checkpoints with a strong preference for the tumor microenvironment (TME). Besides, immunomodulators specifically target the recently discovered inhibitory immune checkpoint, sialic acid-binding immunoglobulin-like lectin (Siglec-15). Distinctive in its molecular composition, Siglec-15 has a unique molecular composition and been shown to be highly prevalent in numerous solid tumor tissues and tumor-associated macrophages (TAMs) in human subjects. Notably, Siglec-15 is up-regulated across various cancer types. As a result, Siglec-15 has attracted significant attention due to its exclusive nature concerning PD-L1 expression, suggesting its role in immune evasion in patients lacking PD-L1. Siglec-15 predominantly appears in certain populations and can promote tumor development by repressing T lymphocyte activation and proliferation, thereby facilitating tumor cell immune escape. Furthermore, Siglec-15 is implicated in osteoclast differentiation and bone remodeling, indicating that it is a promising target for next-generation cancer immunotherapies. Additionally, Siglec-15 can modulate immune responses to microbial infections. The current treatment strategies for hematological conditions predominantly include conventional intensive chemotherapy and transplantation methods. However, emerging immunotherapeutic approaches are increasingly recognized for their overall effectiveness, indicating that specific molecular targets should be identified. The expression of Siglec-15 within tumor cells may indicate a novel pathway for treating hematological malignancies. In this study, the biological attributes, expression patterns, and pathogenic mechanisms of Siglec-15 across various diseases were reviewed. The role of Siglec-15 in the pathogenesis and laboratory diagnosis of hematological disorders was also evaluated. [ABSTRACT FROM AUTHOR]

The leukocyte immunoglobulin-like receptor B (LILRB) proteins, characterized by their transmembrane nature and canonical immunoreceptor tyrosine-based inhibitory motifs (ITIM) signaling, play a pivotal role in maintaining immune homeostasis and are implicated in the pathogenesis of various disease states. This comprehensive review will focus on the intricate involvement of the LILRB family in hematologic malignancies. These receptors have emerged as valuable diagnostic and prognostic biomarkers in leukemia, lymphoma, and myeloma. Beyond their prognostic implications, LILRBs actively shape the immune microenvironment and directly influence the disease pathogenesis of hematologic malignancies. Furthermore, their identification as potential therapeutic targets offer a promising avenue for precision medicine strategies in the treatment of these disorders. Currently, multiple LILRB directed therapies are in the preclinical and clinical trial pipelines. This review underscores the multifaceted role of the LILRB family in hematologic malignancies, highlighting their significance from diagnostic and prognostic perspectives to their broader impact on disease pathophysiology and as valuable therapeutic targets. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) are a critical concern in pediatric onco-hematological patients undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT), leading to a major impact on morbidity, long-term hospitalization, and mortality. We retrospectively analyzed 202 BSIs in 145 patients, consisting of 128 with hematological malignancies, one with a solid tumor, and 16 with non-malignant hematological diseases. We collected data on patient demographics, clinical characteristics, pathogen distribution, and antimicrobial pathogen susceptibility. Gram-positive infections were the most frequent at (58.4%), followed by gram-negative (41%), and fungal infections (0.5%). Particularly, the majority of these infections occurred during the induction phase of chemotherapy, where 94 (46.5%) BSI episodes were recorded, predominantly in neutropenic patients (88.3%). The consolidation phase experienced lower BSIs (11.8%); among these patients (54.1%) were non-neutropenic. BSIs observed in (23.7%) of patients in the maintenance phase, with a higher proportion (66.6%) being neutropenic. Among the 7 patients who underwent HSCT, BSIs occurred in (4.9%) cases, mainly (70%) due to neutropenia. The most prevalent pathogens were Staphylococcus epidermidis (19.8%), Staphylococcus hominis (16.3%), and Escherichia coli (8.4%). The study highlights the critical need for vigilant monitoring and customized infection management strategies to enhance patient outcomes across chemotherapy phases and HSCT. [ABSTRACT FROM AUTHOR]

Objectives: To describe the frequency of neutropenia and Felty syndrome in patients with rheumatoid arthritis (RA) attended in routine clinical practice. Methods: We selected by randomization a sample of 270 RA patients attended from January 2014 to November 2022. Demographic, clinical, and neutropenia-related variables were collected from the electronic medical records. Neutropenia was defined as having an absolute neutrophil count (ANC) of less than 1500/mm3 once, and acute if it persisted for <3 months. Felty syndrome was defined as RA-related neutropenia, rheumatoid factor (RF) and/or anti citrullinated protein antibody (ACPA) positivity. Results: We found 50 patients who had at least one neutropenia episode, with an incidence of 18.5% (14.0–25.6%). Most were women, with age (mean, p25–p75) at the time of neutropenia of 61.5 (57.4–69.3) years, 85% RF+ and 76% ACPA+. The demographic and RA characteristics of patients with and without neutropenia were very similar, except for sex: most patients with neutropenia were women. The 50 patients had 99 episodes of neutropenia; 59% were acute. The lower ANC was 1240 (1000–1395) mm3, and most of the episodes were mild (74%). In 32% of cases, there was other cytopenia. The RA activity measured by DAS28 in patients with neutropenia was low, at 2.18 (1.75–2.97). A total of 82 of 99 neutropenia episodes were related to DMARDs, 60% to Anti-IL6 drugs in monotherapy, 13% to RA activity, 3% to infectious diseases and 1% to hematologic malignancy. There were five (1.8%) cases with Felty syndrome, but only one woman with the classic combination of RA, positivity of autoantibodies (RF and ACPA), neutropenia and splenomegaly. Conclusions: In the 21st century, neutropenia in RA patients is most commonly related to biologics, mostly IL6 inhibitors and methotrexate. Episodes are mild, acute, with low RA activity, and associated with severe infections in few cases. Felty syndrome is rare. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is a hematological disorder characterized by the abnormal proliferation of leukemic cells. This study aims to model the dynamics of leukemic and healthy cell populations in CML, considering the role of the immune system and the effects of treatment with Imatinib. The model also addresses the development of treatment resistance in cells, following the Goldie–Coldman hypothesis. We employ a system of delay differential equations to simulate the interactions between leukemic cells, healthy cells, and the immune system under treatment. The results provide insights into the dynamic balance between leukemic cells, healthy cells, and immune responses, and the impact of developing resistance on treatment outcomes. [ABSTRACT FROM AUTHOR]

This article discusses a case report of fatal thrombotic microangiopathy (TMA) during induction therapy for acute myeloid leukemia in a patient with germline GATA2 haploinsufficiency. The patient experienced severe complications, including hemorrhages and organ dysfunction, leading to her demise. The article highlights the role of GATA2 in maintaining healthy endothelial function and the relatively uncommon vascular manifestations of GATA2 deficiency, such as thrombosis. The study emphasizes the need for further research to understand and mitigate the risk of catastrophic complications in patients with GATA2 deficiency undergoing intensive chemotherapy. [Extracted from the article]

The document explores the structural perturbations in megakaryocytes in patients with primary myelofibrosis and those with a germline RUNX1 mutation. It discusses the role of transcription factors in megakaryocyte differentiation and platelet production, highlighting the importance of cytoskeletal dynamics in this process. The study investigates centrosomal and Golgi organization in patients with myeloid proliferation disorders, revealing abnormalities in protein expression patterns that may impact megakaryocytic morphology and platelet production. The findings suggest common perturbations in microtubular structures in these conditions, emphasizing the need for further research to understand the mechanisms underlying these abnormalities. [Extracted from the article]

Drug package inserts are a crucial foundation for clinical medication practices and serve as the legal basis for guiding rational drug use and ensuring patient safety and efficacy. As rare disease treatments evolve, current package inserts often need to meet the clinical requirements for treating such conditions, frequently resulting in off-label drug use. This consensus is derived from discussions between Guangdong Pharmaceutical Association Hematologic Rare Diseases Group experts. The consensus aims to provide a framework and reference for the clinical application of off-label drug use in treating rare hematologic diseases. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs) are critical for maintaining lifelong blood production and immune function, especially in the context of bone marrow transplantation, where their ability to reconstruct multiple blood lineages is essential. However, recent studies have revealed that certain HSCs exhibit a bias toward platelet differentiation, termed platelet-biased HSCs (P-HSCs). This lineage bias, particularly pronounced with aging, can lead to imbalances in post-transplant blood recovery, negatively affecting patient outcomes. Research by Claus Nerlov's team has provided key insights into the heterogeneity of HSCs, focusing on the age-related expansion of P-HSCs. Using advanced techniques such as single-cell RNA sequencing and molecular barcoding, their work highlights the evolutionary conservation of platelet bias in HSCs across species. This work delves into these findings, discussing their clinical implications for bone marrow transplantation, aging-related blood disorders, and potential therapeutic strategies. Moreover, we address limitations in current methodologies and propose future directions for research to optimize HSC-based therapies and improve clinical outcomes in hematological diseases. [ABSTRACT FROM AUTHOR]

Indolent lymphomas, such as follicular lymphoma and marginal zone lymphoma, are slowly progressing blood diseases. They are typically treated with immunochemotherapy when symptoms arise, allowing for prolonged survival. However, these conditions can lead to multiple relapses, which may gradually result in resistance to treatment, negatively impacting overall prognosis, especially in cases of early relapse after diagnosis. Chimeric antigen receptor (CAR) T-cell therapy has been developed for relapsed indolent lymphomas, with tisagenlecleucel and axicabtagène ciloleucel currently approved in France for use from the third line of treatment in follicular lymphoma. Real-life data support the efficacy and good tolerance of this therapy, even among elderly patients, as observed in phase II studies. These treatments offer hope for high-risk patients facing these challenging lymphomas. [ABSTRACT FROM AUTHOR]

Background: Antithrombin (AT) is a serine protease inhibitor which exerts its anticoagulant effect through binding to serine residues in the active centers of procoagulant serine proteases. Its deficiency is associated with increased risk of venous thrombosis. We aim to investigate the pathogenic mechanism of two natural mutants (W221C and M284R) in inherited AT deficiency. Methods: We analyzed 9 unrelated patients with inherited AT deficiency by extracting peripheral blood DNA and sequencing the SERPINC1 gene after amplification by polymerase chain reaction. Enzyme-linked immunosorbent assay and heparin affinity chromatography were used to assess AT secretion and purification efficiency. The mutant AT models were evaluated via computational simulations. Results: Among the 9 patients with inherited AT deficiency, 8 patients had type I AT deficiency, and one patient had type II AT deficiency with subtype of reactive site mutation. Seven of them experienced venous thrombotic events and all patients were found genetic mutations including missense (n = 6), deletion (n = 2) and insertion (n = 1). Two point mutations, W221C and M284R, were identified and were hypothesized to affect AT by destabilizing the central β-sheet. Based on immunoassays and heparin purification, the W221C mutant may impair AT secretion, whereas M284R mutant decreased the total AT production (696.8 ± 151.6 ng/ml versus 3833.72 ± 315.4 ng/ml, p = 0.029). Both mutants delayed the peak of AT release in heparin affinity chromatography. Conclusions: Our study demonstrates that two mutations in SERPINC1 gene altered the production and structure of AT by in vitro protein expression and functional studies, including protein secretion and production. These findings enhance our understanding of the genetic basis of AT deficiency and its possible clinical implications. [ABSTRACT FROM AUTHOR]

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Background: Sickle cell disease (SCD) is a genetic hematological disorder associated with significant mortality and a range of complex complications that manifest differently across various age groups. Methods: This study aimed to evaluate the demographic, clinical, and laboratory characteristics of SCD patients in Taif City, Saudi Arabia, with a focus on variations among children, adolescents, adults, and middle-aged individuals. A multicenter retrospective cohort study included 129 patients with confirmed diagnosis of SCD between January 2018 to October 2023 and divided into 4 cohorts. The analysis compared hospital stay durations, admission rates, SCD complications, and medication usage. Results: Among the participants, 35 were children (27%), 18 adolescents (14%), 63 adults (49%), and 13 middle-aged individuals (10%). Clinical complications as splenic disease in children (34.3%) were more frequent compared to adolescents (5.6%) and adults (4.8%). Additionally, chronic kidney disease was more prevalent in middle-aged patients (15.4%). Pain was reported in 65.1% of patients, with vascular occlusive crises occurring in 41.1%. Treatment adherence varied, with children showing higher penicillin use (74.3%), while opioid usage was greater in middle-aged patients (76.9%). Conclusions: The findings underscore the necessity for age-specific management strategies in SCD. Further research with larger populations is suggested to enhance the understanding of disease progression and treatment efficacy across different age groups. [ABSTRACT FROM AUTHOR]

Simple Summary: The occurrence of hematologic toxicity is a crucial side effect during definitive radiochemotherapy with cisplatin weekly for locally advanced cervical cancer and is even challenging with the implementation of current studies with intensified systemic therapy regimens. We aimed to assess the course of toxicity profiles of hematotoxicity. In a high-risk cohort of 147 women with 82.3% FIGO stage ≥ III, our results showed the occurrence of a hemoglobin nadir after the fourth chemotherapy cycle, with a median of 36 days after RT initiation. A value below 9 g/dl was associated with inferior local control, while the necessity of transfusion was significantly correlated to overall survival and distant control. Our analysis suggests the need for special patient monitoring from the fourth week onwards, about 30 days after the start of treatment, to guarantee the safe application of radiochemotherapy. Background/Objectives: Definitive radiochemotherapy with concomitant cisplatin 40 mg/m2 weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy. Methods: We retrospectively analyzed 147 patients, who received definitive radiochemotherapy between 2000 and 2019 and evaluated laboratory parameters before, after, and at each chemotherapy cycle to evaluate the occurrence, course, and profile of hematotoxicity. Further, we assessed the impact of hemoglobin levels and transfusion on oncological outcomes. Results: In a high-risk cervical cancer population with 82.3% of women with FIGO ≥ III stage, the 1-, 2-, and 5-year rates of overall survival (OS) were 89.1%, 74.7%, and 63.3%, and local control (LC) rates were 90.1%, 86.1%, and 75.0%, respectively. Grade 3 leukopenia was present in 2.1% and grade 3 anemia in 4.3%. No higher grade ≥ 4 hematotoxicity was observed. Absolute hemoglobin levels significantly reduced after the fourth cycle, with a median time from the start of therapy to hemoglobin nadir of 36 days. A lower hemoglobin nadir (<9 g/dL) was significantly associated with inferior LC. Red blood cell transfusion was applied in 44.9% of the women; the necessity of transfusion was significantly correlated to inferior OS, LC, and distant control. Conclusions: Our results suggest the need for special consideration of increased hematotoxicity and consistent implementation of anemia therapy, particularly from the fourth RT week onwards, to enable full-course definitive radiochemotherapy for locally advanced cervical cancer patients. [ABSTRACT FROM AUTHOR]