Search Results (186)

This study aimed to evaluate the effectiveness of different rehabilitation protocols following osteochondral autograft transplantation (OAT) in patients with focal osteochondral defects of the femoral condyle, using the MOCART 2.0 knee score as a primary imaging outcome. Twenty-nine patients were divided into three groups: Group 1 (n = 9) received OAT with bone marrow aspirate concentrate (BMAC) and a 12-week two-phase rehabilitation program; Group 2 (n = 11) received OAT with a 12-week program without BMAC; and Group 3 (n = 9) received OAT with a shortened 6-week program. At the 12-month follow-up, Group 1 demonstrated a superior cartilage repair quality, with the highest mean MOCART 2.0 score (96.1), compared to Group 2 (80.2) and Group 3 (71.7). Notably, complete defect filling was observed in five patients in Group 1 versus four in Group 2 and only one in Group 3. The integration and surface integrity were also better preserved in Group 1. The addition of BMAC and an extended, progressive rehabilitation protocol significantly enhanced the morphological cartilage repair parameters. These results suggest that a biologically enhanced and prolonged recovery plan may offer a greater structural restoration of cartilage after OAT than conventional or accelerated protocols. Full article

Background and Objectives: Sesamoiditis is a painful and functionally limiting condition that affects the sesamoid bones of the hallux, frequently seen in athletic populations. Despite its clinical relevance, there are no standardised guidelines for its conservative management. This systematic review aims to evaluate the effectiveness of conservative treatments for sesamoiditis by summarising individual-level data from published studies. Materials and Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ISI/Web of Science, and PEDro (Physiotherapy Evidence Database) up to December 2024 in accordance with PRISMA 2020 guidelines and following a protocol specifically devised for rare or underrepresented medical conditions. Eligible studies included case reports and case series involving patients aged ≥16 years who were conservatively treated for clinically and/or radiologically diagnosed sesamoiditis. Data on patient demographics, diagnosis, type and duration of treatment, pain- (Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS)) and function-related (Foot and Ankle Ability Measure (FAAM) and Foot and Ankle Outcome Score (FAOS)) outcomes, and return to activity were extracted. Study quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Pooled effect sizes were computed where applicable. Results: Out of 2380 initial records, 11 studies comprising 59 patients (29 females) were included. Treatments varied widely, including orthotics, corticosteroid injections, physical therapy, and biologic approaches such as concentrated bone marrow aspirate (CBMA). VAS scores improved in 66% of cases. NRS scores returned to baseline in some patients after initial improvement, revealing recurrence. FAAM and FAOS subscales showed functional improvements, particularly in sports-specific domains. Return to activity varied: in a case series, 45.4% resumed pain-free sports participation, while others remained symptomatic. Conclusions: Conservative treatment options for sesamoiditis showed variable effectiveness with promising outcomes in selected patients. Corticosteroid injections and orthotics appeared beneficial, but high recurrence and limited functional recovery persisted in some cases. Standardised treatment protocols and high-quality prospective studies are needed to improve clinical decision-making and optimise non-surgical management. Full article

Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants. Full article

Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (n = 67) or recurrent (n = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (n= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (n = 75 cells). The occurrence of CK- DTCs (n = 69) was significantly correlated to PD-L1 (r = −0.305, p < 0.01) and HER2 positivity (r = −0.234, p < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy. Full article

Background/Objectives: Nontuberculous mycobacteria (NTM) represent a heterogeneous group of pathogens with increasing global prevalence and significant geographical variation in species distribution. NTM infections, often affecting immunocompromised individuals, are difficult to diagnose due to nonspecific clinical presentations and laboratory findings. This case study presents a rare extrapulmonary NTM infection in a 73-year-old man, initially misdiagnosed as sarcoidosis, highlighting the diagnostic and therapeutic challenges posed by such infections. Methods: The patient, a pigeon fancier, presented with recurrent fever and pancytopenia. Extensive diagnostics included blood cultures, bone marrow aspiration, and histopathology. Initial cultures and serological tests remained negative. Results: Bone marrow aspiration revealed epithelioid granulomas, initially leading to the provisional diagnosis of sarcoidosis. However, after six weeks, M. genavense was isolated from mycobacterial blood cultures from bone marrow aspirant. Antimicrobial therapy with azithromycin, rifampicin, and ethambutol was initiated. Following the initiation of appropriate antimycobacterial therapy, the patient developed immune reconstitution inflammatory syndrome (IRIS), which was managed with supportive care. The patient’s condition improved, and no further febrile episodes occurred post-treatment, marking the successful conclusion of NTM therapy. Conclusions: This case underscores the diagnostic complexity of extrapulmonary NTM infections, particularly in immunocompromised patients. Misdiagnosis can delay appropriate treatment. M. genavense, though rare, should be considered in patients with a fever of unknown origin, especially with a background of immunosuppression. Prompt mycobacterial testing and tailored antibiotic therapy are crucial to improving outcomes in NTM infections. Full article

Red blood cells (RBCs) have traditionally been excluded from orthobiologic formulations due to inflammation, oxidative stress, and hemolysis concerns. However, emerging evidence suggests that RBCs may play an active role in regenerative medicine, contributing to immune modulation, vascular support, and oxidative balance. Their interactions with macrophages, involvement in nitric oxide signaling, and release of extracellular vesicles suggest they may influence tissue repair more than previously assumed. Despite these potential benefits, RBC retention in orthobiologic preparations like platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) remains controversial, with most protocols favoring their removal in the absence of robust translational clinical data. This review explores the biological functions of RBCs in regenerative medicine, their potential contributions to PRP and BMAC, and the challenges associated with their inclusion. While concerns about hemolysis and inflammation persist, controlled studies are needed to determine whether selective RBC retention could enhance musculoskeletal healing in some scenarios. Future research should focus on optimizing RBC processing techniques and evaluating their impact on clinical applications. Addressing these gaps will clarify whether RBCs represent an overlooked but valuable component in regenerative therapies or their exclusion remains justified. Full article

Visceral leishmaniasis (VL) is a severe parasitic disease caused by Leishmania spp., with a significant impact on pediatric populations, particularly in endemic regions. The diagnosis of VL in children requires a high index of suspicion, as clinical manifestations—such as prolonged fever, hepatosplenomegaly, and pancytopenia—overlap with other infectious and hematologic diseases. While serological and molecular tests aid in detection, bone marrow aspiration remains the gold standard for definitive diagnosis. In this case series, we describe five pediatric patients diagnosed with VL in Italy, emphasizing the importance of a timely and accurate diagnostic approach. Liposomal amphotericin B (LAmB) is the first-line treatment in Southern Europe due to its high efficacy and reduced toxicity. Our patients received a standard regimen of 3 mg/kg daily for five days, plus an additional dose on day 10, leading to rapid clinical improvement. However, some cases required supportive care, such as red blood cell transfusions, particularly in patients with co-infections. Despite being a neglected disease, VL is re-emerging in Europe, influenced by climate change, increased pet ownership, and migration from endemic regions. Prevention strategies focus on vector control, canine vaccination, and public health awareness. The global rise in pediatric VL highlights the need for improved surveillance, access to affordable treatments, and the development of effective vaccines to mitigate the disease burden in both endemic and non-endemic areas. Full article

Background: Seasonal influenza viruses are primarily known for causing respiratory illness, but rare hematologic complications can occur, especially in young children. While influenza A is more commonly linked to severe manifestations, influenza B can similarly precipitate life-threatening cytopenias, particularly in toddlers. Case Presentation: We report the case of a previously healthy 1-year-and-8-months-old girl who presented with a high fever, cough, and marked pallor during peak influenza season. Laboratory tests revealed significant microcytic, hypochromic anemia and severe thrombocytopenia. Rapid antigen testing was positive for influenza B. An extensive workup for other causes of bicytopenia, including leukemia, hemolysis, aplastic anemia, and other viral infections, yielded negative results. The child was managed with urgent red blood cell and platelet transfusions, oseltamivir antiviral therapy, broad-spectrum antibiotics, corticosteroids, and supportive care. Bone marrow aspiration was deferred in light of the rapid hematologic recovery. Her hemoglobin greatly improved, and her platelet count reached normal values at discharge. Conclusions: Our case underscores the need to consider influenza in the differential diagnosis of unexplained cytopenias during flu season. This case illustrates that influenza B can mimic hematologic malignancies. Rapid diagnosis and supportive treatment are essential to avoid fatal outcomes. Influenza vaccination plays a significant role in preventing severe complications, such as those we encountered. Full article

Background/Objectives: Chronic idiopathic thrombocytopenic purpura (chITP) is an autoimmune disease which develops in 10–30% of patients with newly diagnosed idiopathic thrombocytopenic purpura (ndITP). It is defined as thrombocytopenia which lasts longer than 12 months, with extremely diverse clinical expressions. The aim is to present the most significant clinical and laboratory characteristics of children with chITP. Methods: This is retrospective, observational research, which included children between 2–18 years with chITP who were treated in the Republic of Serbia for 25 years. We analyzed clinical data from personal and family medical histories and different laboratory analyses. Results: The total number of respondents was 152, with female predominance (F:M = 1.27:1) and mild predominance of adolescents. Of the patients, 15% were asymptomatic, but 15% had periodically life-threatening bleeding. Transfusion was not required for 70% of patients. Thirty-five percent of patients had chITP alone, and 45% had high titer levels of autoantibodies. The most frequent comorbidity was Hashimoto thyroiditis (15%). The same percentage (45%) of family members were reported with and without autoimmune diseases. Twenty-five percent of patients were resistant to initial therapy. Helicobacter pylori was detected in 20%, 70% had higher levels of lactate dehydrogenase (LDH), three patients had sufficient serum vitamin D levels, splenomegaly was found in 25%, and accessory spleen in 14% of patients. Around 50% of patients had a platelet count between 20–50 × 10⁹/L, and 40% below 20 × 10⁹/L. Mean platelet volume (MPV) was 10.6 ± 1.4 fL. No dysplastic changes were noted in bone marrow aspirate. Initial first-line therapy was sufficient for 45% of patients, second-line therapy was administered in 25%, splenectomy was performed in 20%, and 10% received all available treatments. Conclusions: The severe clinical form of pediatric chITP is accompanied by a low platelet count, the presence of autoimmune comorbidities, a positive family medical history, resistance to initial therapy, hypovitaminosis D, and rare megakaryocytes in the bone marrow. Full article

Bone marrow aspirate concentrate (BMAC) is an autologous regenerative therapy enriched with mesenchymal stem cells (MSCs) and bioactive growth factors, offering potential disease-modifying effects in knee osteoarthritis (OA). Compared to conventional intra-articular treatments, including hyaluronic acid (HA), platelet-rich plasma (PRP), and corticosteroids, BMAC promotes cartilage regeneration, modulates inflammation, and enhances subchondral bone remodeling. Clinical evidence suggests that BMAC provides short- to mid-term symptomatic relief and functional improvement, with some studies indicating a potential to delay total knee arthroplasty (TKA). However, findings remain inconsistent, and long-term efficacy compared to PRP or autologous conditioned serum (ACS) is yet to be firmly established. Variability in BMAC preparation methods, injection protocols (single vs. repeated administration, intra-articular vs. subchondral delivery), and patient selection criteria complicates its clinical application, highlighting the need for standardized guidelines. Additionally, economic feasibility and cost-effectiveness concerns limit its widespread adoption. This review synthesizes current clinical evidence, evaluates optimal administration strategies, and explores future directions for improving treatment standardization and patient-specific therapy. Future research should prioritize well-designed, multicenter randomized controlled trials (RCTs) with long-term follow-up to confirm the sustained efficacy and therapeutic potential of BMAC in OA management. Full article

Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. Objectives: This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and TP53 mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Results: Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; p = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; p = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Conclusions: Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment. Full article

Despite the progress made in recent years in hematological diagnostics, cytological assessment of bone marrow, including the assessment of megakaryocytes, is still an important element of the diagnostic process. It is one of the most accurate methods for detecting even minor abnormalities, which is often superior to histopathological examination in this respect. Although, according to current recommendations, megakaryocytes are not included in the total percentage formula of the myelogram, the assessment of platelet function, morphological features, and quantitative disorders allows for the direction of further diagnostic process. In this article, we present the principles of assessing megakaryocytes in a bone marrow aspirate smear. We also characterize normal megakaryocytes at various stages of megakaryopoiesis, atypical megakaryocytes in pathological and physiological conditions, and cells with a similar morphology to megakaryocytes. Full article

Background: The diagnosis of hematologic neoplasms is usually based on a synopsis of the peripheral blood (PB) and bone marrow findings. Morphology continues to be the cornerstone, but genetic analysis plays an increasingly important role. In routine workup, molecular genetic analysis is performed from a bone marrow aspirate (BMA). In the event of inadequate aspiration, PB is used. Not infrequently, however, PB only partially represents the disease. In this situation, molecular genetic analysis of formalin-fixed and paraffin-embedded (FFPE) bone marrow core biopsy (BMCB) could be a better alternative than PB. However, no systematic correlation of genetic findings from BMCB with results from BMA and PB has been reported. Methods: Therefore, BMCB obtained during routine diagnostics were subjected to post hoc molecular genetic analysis using next generation sequencing (NGS). The identified molecular genetic alterations were then compared with data within routine diagnostics of the corresponding BMA and/or PB. Results: In total, 29 BMCB and corresponding BMA samples were analyzed, and in 12/29 cases PB was additionally available. The analysis of BMCB and BMA showed identical results in 17 cases, but BMCB revealed a gain of information in 11, while in only 1 case, BMCB failed to identify the mutations in comparison to BMA. Conclusions: Despite the small numbers, molecular genetic analysis of bone marrow core biopsy using next generation sequencing could detect relevant additional gene mutations compared to bone marrow aspirate and/or peripheral blood. Full article

Megakaryocytes (MKs) are rare, large, polyploid bone marrow (BM) cells responsible for the production of platelets. The identification and characterization of MKs is widely recognized as challenging. Manual microscopy is especially difficult due to the rarity and complex morphology of MKs, while flow cytometry faces additional challenges from MKs’ large size, fragility, and platelet adhesion, causing false positives. We present a novel approach to accurately enrich MKs from human BM aspirates with a specific focus on the detection and quantification of microMKs. By integrating CD41⁺ cell enrichment, immunophenotyping, and morphometric analysis, we identified cells of the megakaryocytic lineage. To increase accuracy, a convolutional neural network was trained to identify CD41⁻ cells falsely displaying an MK-like immunophenotype due to adhesive CD41⁺ platelets. This allowed for exclusion of 94.9% of false positive events, considerably enhancing specificity. CD41 positive enrichment prior to imaging flow cytometry acquisition increased the MK frequency nearly 200-fold, yielding a population of both mature and immature MKs, thus supporting analysis of MK progenitors. Overall, this advanced approach enables enrichment of MKs from human BM, considerably increasing the accuracy and statistical power of the MK analysis. This may provide an important addition in the context of MK-related diagnostics and research. Full article

Digital morphology (DM) analyzers have advanced clinical hematology laboratories by enhancing the efficiency and precision of peripheral blood (PB) smear analysis. This review explores the real-world application of DM analyzers with their benefits and challenges by focusing on PB smear analysis and less common analyses, such as bone marrow (BM) aspirates and body fluids (BFs). DM analyzers may automate blood cell classification and assessment, reduce manual effort, and provide consistent results. However, recognizing rare and dysplastic cells remains challenging due to variable algorithmic performances, which affect diagnostic reliability. The quality of blood film as well as staining techniques significantly influence the accuracy of DM analyzers, and poor-quality samples may lead to errors. In spite of reduced inter-observer variability compared with manual counting, an expert’s review is still needed for complex cases with atypical cells. DM analyzers are less effective in BM aspirates and BF examinations because of their higher complexity and inconsistent sample preparation compared with PB smears. This technology relies heavily on artificial intelligence (AI)-based pre-classifications, which require extensive, well-annotated datasets for improved accuracy. The performance variation across platforms in BM aspirates and rare-cell analysis highlights the need for AI algorithm advancements and DM analysis standardization. Future clinical practice integration will likely combine advanced digital platforms with skilled oversight to enhance diagnostic workflow in hematology laboratories. Ongoing research aims to develop robust and validated AI models for broader clinical applications and to overcome the current limitations of DM analyzers. As technology evolves, DM analyzers are set to transform laboratory efficiency and diagnostic precision in hematology. Full article