To describe principles of ultrasound-guided injection techniques for intralesional delivery of regenerative orthobiologics into equine tendon and ligament core lesions. A university-owned horse and equine cadaver forelimbs. A reproducible protocol for ultrasound-guided injection is demonstrated with the superficial digital flexor tendon used as an example. Following diagnosis of the lesion, the horse should be sedated and the affected limb desensitized with perineural anesthesia. The lesion is identified ultrasonographically in transverse and longitudinal planes, marked externally, and aseptically prepared. Under sterile conditions, the needle is placed through the skin, viewed on ultrasound, advanced to the lesion's hypoechoic core or region of fiber disruption, and stabilized during attachment of the syringe and subsequent injection. Injectate volume is governed by product type and lesion size, with platelet-rich plasma (PRP), bone marrow aspirate concentration (BMAC), mesenchymal stem cells (MSCs), and autologous conditioned serum or protein solution (ACS/APS) representing the most commonly used equine orthobiologics. Ultrasound monitoring throughout the injection confirms intralesional placement and dispersion of the injectate. Ultrasound guidance enables precise intralesional placement and real-time observation of injectate dispersion. Current clinical opinion suggests injecting tendon/ligament injuries during the sub-acute phase or within a few weeks of injury. The technique minimizes iatrogenic trauma and improves delivery accuracy for regenerative treatments. Ultrasound-guided intralesional injection is an accessible and effective method to enhance the precision, safety, and therapeutic success of orthobiologic delivery in equine tendon and ligament injuries.

Ningxue shengban decoction regulates T-cell immune balance in immune thrombocytopenia via the bone marrow hematopoietic microenvironment.

Baiting-enhanced extravasation of lipid nanoparticles for targeted co-delivery of decitabine and siTNF-α to the bone marrow niche in leukemia therapy.

The purpose of this study is to enable 3D abdominal imaging and quantitative parameter mapping in free breathing conditions and simultaneously provide proton-density fat fraction (PDFF), water-specific and fat-specific T1 maps. A radially encoded MP2RAGE with alternated fat and water selective pulses was implemented and validated on a phantom containing gadolinium (Gd) and pork fat at different concentrations. Comparison with MR spectroscopy and imaging techniques of reference was performed invitro. Multiple experiments were carried out on healthy volunteers and individuals with a record of liver disease and benign bone marrow lesions to evaluate the method's repeatability, accuracy and potential for clinical application. Invitro water or fat specific T1 was in agreement with estimates provided by reference methods over a wide range of mixture ratios. PDFF was strongly correlated with spectroscopy (Pearson coefficient of 0.98) and other imaging techniques although underestimated due to the imperfect pulse selectivity profile. Images free of ghosting artefacts were acquired invivo on seven volunteers. The whole abdomen was imaged, as well as a large part of the spine (from T11 to L5). Parametric maps provided repeatable estimates in the liver, the bone marrow and the subcutaneous fat that were consistent with values reported in literature and other imaging techniques. The acquisition time could be halved without significantly affecting the quantitative values. Overall, high-contrast MP2RAGE abdominal images, water- and fat- specific T1 maps and PDFF maps were achieved in a single 3D acquisition under free breathing.

Splenic B-cell lymphoma/leukemia includes a group of indolent small B-cell lymphomas/leukemias that share overlapping morphological and immunophenotypic features, making accurate diagnosis challenging. Specific gene rearrangements have not been commonly associated with splenic B-cell lymphomas/leukemias, and the TCL1 gene rearrangement-characteristic of T-cell prolymphocytic leukemia-has not been previously reported in B-cell lymphomas/leukemias. Here, we report two unique cases of splenic B-cell lymphoma/leukemia harboring an IGH::TCL1 rearrangement. Patient #1 was a 74-year-old man with a 25-year history of low-grade B-cell leukemia involving the peripheral blood, spleen, and bone marrow. Patent #2 was a 54-year-old woman who recently presented with lymphocytosis and low-level bone marrow involvement. Both patients were asymptomatic and incidentally found to have lymphocytosis. The neoplastic cells in both cases displayed polar villous cytoplasmic projections, were of B-cell lineage, and were negative for CD5 and CD10. Notably, an IGH::TCL1 fusion was identified in both cases. The identification of IGH::TCL1 fusion in these two cases of splenic B-cell lymphoma/leukemia suggests that TCL1 gene rearrangements can occur in B-cell lymphoma/leukemia and should not be considered exclusive to T-cell prolymphocytic leukemia. Accurate diagnosis of splenic B-cell lymphoma/leukemia with TCL1 rearrangement requires evaluation of morphologic and immunophenotypic features and genetic assessment of TCL1.

Elevated vitamin B12 concentration can be caused by supplementation, liver disease, kidney disease, or myeloid malignancies. Persistent, unexplained elevations of vitamin B12 can raise concern among patients and may lead to invasive diagnostic procedures, including bone marrow biopsy. A potential benign cause of this elevation is macro-B12, a complex of vitamin B12, transcobalamin, and immunoglobulins. Although not bioactive, this complex can cause elevated plasma vitamin B12 concentrations due to reduced clearance. Polyethylene glycol (PEG) precipitation is a laboratory technique that can be used to support the suspicion of macro-B12. Here, a case is described in which a PEG precipitation could potentially have prevented an unnecessary bone marrow biopsy. In addition, the presence of macro-B12 was studied in a group of patients with and without myeloid malignancies. Macro-B12 was identified in 24% of 72 individuals with vitamin B12 > 1476 pmol/L. In one of these patients, a functional vitamin B12 deficiency was confirmed by an elevated methylmalonic acid (MMA) concentration. Macro-B12 was not detected in 8 patients with a myeloid malignancy. These findings suggest that, in patients with persistently elevated vitamin B12 concentrations and a low suspicion of a myeloid malignancy, PEG precipitation may help to explain the elevated vitamin B12 and prevent unnecessary diagnostic procedures including bone marrow punctures.

Neutrophils are short lived innate immune cells, critical for pathogen control. They are the most abundant type of leucocyte in the circulation and, in response to inflammatory stimuli, are rapidly recruited into the tissues with the circulating population being replenished from the bone marrow. Although traditionally considered simplistic antimicrobial cells with limited heterogeneity, recent studies have highlighted the diversity of neutrophil phenotypes and their potential as therapeutic targets. Neutrophils rewire their metabolism in response to nutrient availability and inflammatory cues in order to function in diverse, and often hostile, inflammatory environments. In this review we highlight how metabolism fuels neutrophil effector function in diverse tissues and how this can impact disease processes including infection, inflammation and malignancy but also presents novel therapeutic targets.

Exercise rejuvenates bone marrow mesenchymal stem cells associated with the inhibition of inflammatory factors and senescence-related factors.

Age-related GSS promoter methylation in BMSCs drives osteoporosis and the reversal by targeted GSH delivery.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the rapid proliferation of immature white blood cells in the bone marrow. Early and accurate diagnosis is essential for improving clinical outcomes; however, distinguishing between lymphocytes and lymphoblasts poses significant challenges owing to their subtle morphological similarities. Traditional manual diagnostic methods, which rely on expert evaluations, are inherently time-consuming and subject to human error. In recent years, machine learning and deep learning approaches have emerged as promising tools for automating and enhancing diagnostic processes. This review systematically examines state-of-the-art traditional and deep learning techniques applied for ALL detection and classification. We provide a comprehensive analysis of various methodologies, including supervised machine learning algorithms and advanced deep learning architectures, with a focus on critical stages such as image preprocessing, feature extraction, and blast cell quantification. Furthermore, we discuss the performance metrics and accuracy benchmarks, highlighting the potential of these techniques to match or exceed human diagnostic capabilities. The review concludes with a discussion of the current challenges, recent developments, and future directions in the application of artificial intelligence for ALL diagnosis, underscoring the need for continued innovation to meet emerging clinical demands.

Italian register of therapeutic apheresis: 30 years of activity.

Psychosocial factors play a critical role in transplant candidacy, adherence, and clinical outcomes. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) provides a multidimensional framework for psychosocial evaluation; however, comparative evidence across different transplant indications and its associations with symptom and quality-of-life measures remain limited. This study aimed to characterize psychosocial risk profiles across transplant indications using the SIPAT and to examine their associations with sociodemographic, clinical, and psychosocial variables in routine clinical practice. We conducted a cross-sectional observational study involving 176 adult transplant candidates (liver, kidney, lung, heart, bone marrow). Psychosocial functioning was assessed using the SIPAT alongside measures of psychological symptoms, substance use, and quality of life. Group comparisons and hierarchical regression analyses were performed to examine associations between SIPAT scores and aforementioned variables. The median total SIPAT score was 16.0 (IQR 10.0-22.5); 28.4% of candidates were classified as high psychosocial risk, most frequently among liver transplant candidates (44.1%). In hierarchical linear regression, higher alcohol use (β=0.509, p<0.001), greater depressive symptom severity (β=0.226, p=0.033), and lower education (β=-0.182, p=0.003) independently predicted higher SIPAT scores. In hierarchical logistic regression, alcohol use (OR=2.20, p<0.001) and lower education (OR=0.75, p=0.007) independently predicted high psychosocial risk. Domain-level SIPAT assessment provides a structured and clinically informative approach to identifying psychosocial vulnerability across transplant indications, highlighting alcohol use and lower education as key targets for pre-transplant evaluation and support.

Isoeugenol suppression of osteoporosis by modulating macrophage M1 Polarization via p38 MAPK and arachidonic acid metabolism pathways.

Pulsed electromagnetic field drives osteogenic and suppresses adipogenic differentiation of bone marrow mesenchymal stem cells via Wnt/β-catenin signaling to ameliorate osteoporosis.

Sulfated polysaccharide prevents senescent adipocyte-driven osteonecrosis by stem cell fate reprogramming.

Canine Leishmaniasis is a vector-borne zoonotic disease caused by several species of protozoa of the genus Leishmania. In the state of Rio de Janeiro (RJ), Leishmania braziliensis is the most prevalent species causing tegumentary leishmaniasis (TL) and Leishmania infantum is the main causative agent of visceral leishmaniasis (VL). Dogs are the main reservoirs of L. infantum and can be infected with other Leishmania species; however, their role as a reservoir for these species is still poorly understood. There are few epidemiological studies characterising Leishmania at the species level in isolates from dogs in the state of RJ and analysing their geospatial distribution. This work aimed to perform the taxonomic characterisation of Leishmania isolates, obtained from 565 dogs diagnosed between 2000 and 2015 in a reference centre for infectious diseases in RJ, Brazil. Dogs with a positive parasitological diagnosis by invitro culture of different biological samples (intact skin, skin lesion, bone marrow, spleen, lymph node and others) were included. The characterisation of Leishmania species was carried out using multilocus enzyme electrophoresis technique. The dogs' home addresses were individually georeferenced. Thematic and heat maps were created in the QGIS software with cases and the distribution of characterised species. The dogs clinically evaluated (n = 236) were classified as asymptomatic (n = 93; 39.4%), oligosymptomatic (n = 92; 39%), or polysymptomatic (n = 51; 21.6%). A total of 518 Leishmania isolates from dogs were characterised by MLEE as L. infantum (n = 456; 88%) and L. braziliensis (n = 62; 12%), which were obtained by cultivating biological samples from different canine sites. Heat maps identified Barra Mansa as an area of intense VL transmission and Rio de Janeiro and Maricá as municipalities with intense TL transmission. This study contributed to the knowledge of the taxonomic characterisation and geospatial distribution of Leishmania species responsible for canine leishmaniasis in the state of RJ, considering the case series from a reference centre for the diagnosis of leishmaniasis in the state of RJ, Brazil.

PD-1 high expression in T lymphocytes correlates with decreased survival in childhood B-cell precursor acute lymphoblastic leukemia.

Hematopathology workflows are complex, since they include numerous data points necessary for guiding further testing, diagnosis, and patient management. The workflows start with complete blood cell counts, with subsequent morphologic evaluation of peripheral blood (PB) and bone marrow (BM). Digital pathology has the potential to revolutionize PB and BM assessment through the implementation of artificial intelligence for assisted and automated evaluation, but there remain major hurdles toward this ultimate goal, such as lack of regulatory oversight, data standardization, insufficient knowledge and training, and resistance to change, among others. This article reviews the current state of digitalization in the hematopathology practice, recent research using machine learning models for automated specimen analysis, outlines the advantages and barriers facing clinical implementation of artificial intelligence, and offers prospective artificial intelligence-driven clinical workflows for efficient and comprehensive clinical workup.

Bone marrow SELENOP+ macrophages support hematopoiesis after transplantation via GAS6-AXL signaling pathway.

<h2>Abstract</h2><h3>Background</h3> Childhood cancer survival rates have improved over the last decades. Nevertheless, childhood cancer treatment is associated with painful interventions needed for disease monitoring or treatment. It is therefore crucial to ensure appropriate pain control for painful interventions. This European survey aims to map the approaches to manage such interventions in children and adolescents with cancer. <h3>Methods</h3> An online survey was sent to members of the European Society of Paediatric Oncology, asking the way potentially painful interventions are being managed. Interventions included lumbar puncture, bone marrow aspiration and biopsy, removal of drainages, insertion and removal of central venous lines, puncture of porth-a-cath or Ommaya reservoir, tumour biopsy, and insertion of nasogastric tube. Proposed approaches to pain management included local analgesia, systemic analgesia alone, systemic analgesia with sedation administrated by paediatric oncologists or anaesthesiologists, distraction techniques, and other methods. We further asked about drugs used and types of distraction. <h3>Results</h3> A total of 326 health care professionals responded, representing 37 countries. The proportion of participants reporting that an intervention is performed without any pain management ranged from one participant each for bone marrow aspiration/biopsy and tumor biopsy (0,3%), to 101 participants (31%) for nasogastric tube insertion. The intensity of analgesia or depth of sedation per intervention is heterogeneous, so are the drugs used. <h3>Conclusion</h3> The heterogenous results in use of analgesia or sedation during procedures indicate an unmet need. These results highlight the need for guidelines and their implementation in clinical practice. No child or adolescent undergoing cancer treatment should suffer from procedure-related pain.