Bone Marrow Infiltration Research Articles

Radiological and morphological characteristics of the femoral head osteonecrosis in type I Gaucher disease.

BACKGROUND: Osteonecrosis of the femoral head in Gaucher disease typeI is an irreversible bone manifestation of the disease. The cause and mechanisms of osteonecrosis in Gaucher disease are still unknown, and their clinical and radiological characteristics must be taken into account when choosing treatment strategy. AIM: To analyze the radial and morphological changes in the proximal femur after osteonecrosis of the femoral head in typeI Gaucher disease. MATERIALS AND METHODS: The study included 251adult patients with typeI Gaucher disease from the Russian National Registry; histological examination of 22removed femoral bone fragments obtained during total hip replacement in 20patients with Gaucher disease and 9 in patients of the control group was performed. RESULTS: Osteonecrosis of the femoral head is detected in 30% of adult patients with Gaucher disease, and in 20% of patients it lead to femoral head collapse. Spongy bone osteosclerosis of the metaphysis, expansion/swelling of the bone marrow cavity with secondary osteopenia and osteoporosis of the proximal femur were often accompanied by osteonecrosis of the femoral head, creating technical difficulties during surgery. The histological picture revealed a picture of chronic bone ischemia of the proximal femoral metaepiphysis, which was confirmed by the identification of common areas of osteosclerosis during X-ray and MRI examination. Bone marrow infiltration by Gaucher cells in histological preparations persisted regardless of the duration of enzyme replacement therapy against the background of preserved regenerative potential of bone tissue. CONCLUSIONS: Тhe revealed features of the X-ray, MRI and histological picture should be taken into account when planning and conducting orthopedic operations for osteonecrosis of the femoral head in patients with type I Gaucher disease.

Allogeneic CD33-directed CAR-NKT cells for the treatment of bone marrow-resident myeloid malignancies

Chimeric antigen receptor (CAR)-engineered T cell therapy holds promise for treating myeloid malignancies, but challenges remain in bone marrow (BM) infiltration and targeting BM-resident malignant cells. Current autologous CAR-T therapies also face manufacturing and patient selection issues, underscoring the need for off-the-shelf products. In this study, we characterize primary patient samples and identify a unique therapeutic opportunity for CAR-engineered invariant natural killer T (CAR-NKT) cells. Using stem cell gene engineering and a clinically guided culture method, we generate allogeneic CD33-directed CAR-NKT cells with high yield, purity, and robustness. In preclinical mouse models, CAR-NKT cells exhibit strong BM homing and effectively target BM-resident malignant blast cells, including CD33-low/negative leukemia stem and progenitor cells. Furthermore, CAR-NKT cells synergize with hypomethylating agents, enhancing tumor-killing efficacy. These cells also show minimal off-tumor toxicity, reduced graft-versus-host disease and cytokine release syndrome risks, and resistance to allorejection, highlighting their substantial therapeutic potential for treating myeloid malignancies.

Evaluation of the correlation coefficient to determine the severity of bone marrow infiltration between bone marrow burden, fat fraction and Lyso GL1 in adult patients with Gaucher disease. A Study from the Argentine group for the diagnosis and treatment of GD

Evaluation of the correlation coefficient to determine the severity of bone marrow infiltration between bone marrow burden, fat fraction and Lyso GL1 in adult patients with Gaucher disease. A Study from the Argentine group for the diagnosis and treatment of GD

Blastic plasmacytoid dendritic cell neoplasm: a Swiss case series of a very rare disease and a structured review of the literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease, with unique diagnostic challenges and often dismal outcome. There are no widely accepted treatment guidelines available. Lymphoma-like regimens with or without autologous or allogenic transplantation were the cornerstone of most therapeutic concepts. A few years ago, the CD123-directed immunoconjugate tagraxofusp emerged as a new valuable treatment option. The goal of our research was to collect available data on BPDCN-patients treated at large centres in Switzerland and worldwide and to draw conclusions regarding the incidence, clinical presentation, prognostic factors and therapeutic strategies. We collected data from BPDCN patients from leading Swiss haemato-oncology centres from 2005 to 2022. Furthermore, we reviewed and analysed the published literature (cohorts and case reports in peer-reviewed journals) from 1997 to 2020 (structured review of the literature). We identified 115 international publications including 600 patients from all over the world. Most of them had very small sample sizes (only ten papers with more than ten patients) and all but one were retrospective or observational respectively. Most included patients were Europeans (n = 385, 64%) and Asians (n = 120, 20%), followed by Americans (n = 90, 15%) and patients from Australia/New Zealand (n = 3) and Africa (n = 2). BPDCN was more common in men with a predominance of 3:1. The median age (n = 414) at diagnosis was 66.5 years ranging from one month to 103 years. Newly diagnosed women were significantly younger than men (median: 62 vs 67 years, mean: 53.4 vs 59.3 years, p = 0.027) and less often had bone marrow infiltration and affected lymph nodes. Upfront allogenic transplantation as well as ALL regimens performed best, with response to first-line therapy clearly associated with better overall survival. The Swiss cohort contained 26 patients (23 males and 3 females) over 18 years (2005-2022). The median age at diagnosis was 68.5 years (range: 20-83). Ten patients underwent upfront stem cell transplantation (seven allogenic and three autologous), at least trending towards a better overall survival than other therapies. With a follow-up of 8 years, the median overall survival was 1.2 years. Eight patients in this cohort were treated with tagraxofusp, which became available in 2020 and was approved by Swissmedic in 2023. Our study confirms that BPDCN is a very rare and difficult-to-treat disease. Underdiagnosis and underreporting in the literature pose further challenges. Symptoms at presentation seem to differ slightly between sexes and reaching a complete remission after first-line treatment remains crucial for a prolonged overall survival. Effective treatment protocols in first line include transplantation regimens (mainly allogenic, potentially also autologous) as well as ALL protocols. In order to understand the significance of tagraxofusp as a bridge to transplant or as a continuous monotherapy in elderly patients, further evaluation with longer follow-up periods is required. In general, analysis of the Swiss patients confirmed the results from the worldwide cohort.

Поражение костей у взрослых пациентов с болезнью Гоше I типа: распространенность, клинические особенности, костно-суставные осложнения и проблемы инвалидизации

BACKGROUND. Although highly effective enzyme replacement therapy (ERT) for Gaucher disease (GD) is accessible and affordable, orthopedic issues in patients appear often to be the main factor leading to their disability. Bone lesions are essentially observed in 100 % of GD patients. The nature and severity of bone and joint changes, however, are reported to be extremely heterogeneous, whereas their incidence and clinical features have until now remained underresearched. AIM. To assess the incidence and clinical value of bone and joint lesions which complicate the course of GD type 1 with bone involvement. MATERIALS & METHODS. This trial enrolled 267 GD type 1 patients aged 17–85 years (median 38 years), who were followed-up at the National Research Center for Hematology from 2004 to 2024. There were 109 men and 158 women. The analysis focused on the following MRI findings: bone marrow infiltration (BMI), Barnett-Nordin cortical index (BNI), bone deformity, osteolytic and osteonecrotic lesions, as well as orthopedic pathologies progressing to disability. RESULTS. BMI was identified in 213/267 (79.8 %) patients. Erlenmeyer flask-like femoral expansion was observed in 95 % patients (n = 254). The mean BNI was 42.9 % (the normal BNI in adult population exceeds 45 %). Low BNI values were associated with osteolytic lesions, disability, and BMI. No significant association of decreased BNI was seen with osteonecroses. The incidence of osteolytic lesions was 11.2 % (n = 30). New osteolytic lesions were reported neither in ERT nor in substrate reduction therapy recipients. Medullary osteonecrosis was detected in 206/267 (77.15 %) patients, and epiphyseal osteonecrosis was identified in 74/267 (27.72 %) patients. Along with osteonecroses, in contrast to osteolytic manifestations, new lesions (n = 8) were reported to occur under long-term (> 5 years) ERT. The rate of bone fractures was 6.7 % (n = 18). In 18 patients, 64 fractures were observed at various locations. Disability associated with bone and joint complications of GD occurred in 58/267 (21.72 %) patients. After reconstructive surgery, including total articular replacement arthroplasties, 37 patients achieved complete functional recovery. CONCLUSION. Bone changes are essentially observed in all adult patients with GD type 1. However, clinical severity and disability of patients depend on secondary bone and joint complications, among them arthroses resulting from epiphyseal osteonecrosis, pathologic fractures, bone and joint infections. These complications developing on effective ERT were identified in 67/267 patients, which accounted for 25 %.

Diagnosis of a case of ocular reactivation in a patient with lymphoplasmacytic lymphoma

Aims/Purpose: Waldenstrom's macroglobulinemia (WM) is a rare hematological neoplasm characterized by lymphoplasmacytic proliferation, monoclonal immunoglobulin M (IgM) production, and bone marrow infiltration. Ocular involvement can be one of the signs of disease activity, and the purpose of this case is to present the ocular manifestations that may occur through a clinical case seen in consultation.Methods: A review was conducted of a case involving a 64‐year‐old male patient seen in the ophthalmology department of our hospital, with no known drug allergies and a personal history of Waldenstrom's macroglobulinemia diagnosed in 2018, currently in remission. The patient presented with progressive visual acuity loss in the left eye in the context of possible vitritis/chorioretinitis. He was treated with trimethoprim, sulfamethoxazole, and prednisone due to the suspicion of a possible infectious cause. Laboratory tests, serologies, a vitreous biopsy, fluorescein angiography, and ocular ultrasound were performed to determine the etiology. A few weeks later, he presented with clinical symptoms of disorientation and behavioral changes, prompting an emergency visit. A brain MRI was performed, revealing a tumoral lesion in the left frontal lobe, suggestive of cerebral lymphoma.Results: After studying and biopsying the brain lesion, the diagnosis of cerebral lymphoma was confirmed, with ocular involvement in the form of vitritis and chorioretinitis as a sign of disease reactivation.Conclusions: Waldenstrom's macroglobulinemia can manifest in various ways, and one of them can be through ocular activity signs such as uveitis (both anterior and posterior), vitritis, retinitis, and chorioretinitis. Therefore, it is necessary to conduct a thorough differential diagnosis through a complete medical history, laboratory tests, serologies, and imaging studies when suspecting a possible disease reactivation.

EBV-associated lymphoadenopathy in a child

Lymphadenopathy is observed in 55% of children under the age of 10 years and the most often it has a bacterial or viral etiology, but it also can manifest as lymphoproliferative diseases or lymphomas. Lymphoproliferative diseases are characterized by uncontrolled growth of lymphocytes with the development of monoclonal lymphocytosis, lymphadenopathy and bone marrow infiltration. Since the Epstein-Barr virus (EBV) has oncogenic potential, it is essential for doctors to be vigilant about generalized persistent lymphadenopathy on the background of chronic persistent Epstein-Barr infection. The purpose of the article is to increase the awareness of doctors of various specialties about the risk of developing EBV-associated lymphoproliferative diseases in children with generalized persistent lymphadenopathy using the example of a clinical case discussion. The article describes a clinical case of a 14-year-old patient with persistent lymphadenopathy on the background of chronic Epstein-Barr infection. Immunohistochemical study of the lymph node biopsy revealed reactive hyperplasia with expressed immune blast transformation, the presence of CD30-positive cells while excluding Hodgkin lymphoma. It is recommended to involve a multidisciplinary team to prescribe appropriate antiviral therapy, regularly monitor the clinical course, dynamics of laboratory and immunological indicators. The result of the study is the recommendation to repeat biopsy in the absence of positive dynamics in patients with persistent Epstein-Barr infection and lymphadenopathy.

Sensitive liquid biopsy monitoring correlates with outcome in the prospective international GPOH-DCOG high-risk neuroblastoma RT-qPCR validation study.

Liquid biopsies offer less burdensome sensitive disease monitoring. Bone marrow (BM) metastases, common in various cancers including neuroblastoma, is associated with poor outcomes. In pediatric high-risk neuroblastoma most patients initially respond to treatment, but in the majority the disease recurs with only 40% long-term survivors, stressing the need for more sensitive detection of disseminated disease during therapy. To validate sensitive neuroblastoma mRNA RT-qPCR BM testing, we prospectively assessed serial BM samples from 345 international high-risk neuroblastoma patients, treated in trials NB2004 (GPOH) or NBL2009 (DCOG), using PHOX2B, TH, DDC, CHRNA3, and GAP43 RT-qPCR mRNA markers and BM GD2-immunocytology. Association between BM-infiltration levels and event-free survival (EFS) and overall survival (OS) was estimated by using Cox regression models and Kaplan-Meier's methodology. BM infiltration >10% by RT-qPCR at diagnosis was prognostic for survival (adjusted hazard ratio (HR) 1.82 [95%CI 1.25-2.63] and 2.04 [1.33-3.14] for EFS and OS, respectively). Any post-induction RT-qPCR positivity correlated with poor EFS and OS, with a HR of 2.10 [1.27-3.49] and 1.76 [1.01-3.08] and 5-years EFS of 26.6% [standard error 5.2%] versus 60.4% [6.7] and OS of 43.8% [5.9] versus 65.7% [6.6] for RT-qPCR-positive patients versus RT-qPCR-negative patients. In contrast, post-induction immunocytology positivity was not associated with EFS or OS (HR 1.22 [0.68-2.19] and 1.26 [0.54-2.42]). This study validates the association of not clearing of BM metastases by sensitive RT-qPCR detection with very poor outcome. We therefore propose implementation of RT-qPCR for minimal residual disease testing in neuroblastoma to guide therapy.

Clinical outcomes and safety of CAR-T cells in treatment of T-Cell acute lymphoblastic leukemia/lymphoma.

Relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are frequently aggressive and associated with unfavorable prognoses. Pan-targeted Chimeric Antigen Receptor (CAR) T-cell therapy have shown promising results in clinical trials. In recent years, CD7 CAR T-cell and CD5 CAR T-cell demonstrate effectiveness in treating r/r T-ALL/LBL patients with bone marrow infiltration. However, nearly half of r/r T-ALL/T-LBL patients are accompanied by extramedullary disease (EMD), where comprehensive data on the efficacy and safety of CAR T-cell therapy remain limited. Additionally, CD7 CAR T-cell and CD5 CAR T-cell therapy can cause severe immunodeficiency and hematologic toxicity, complicating with difficult immune reconstitution. This review provides an in-depth analysis of the safety profile and adverse events associated with CAR T-cell therapy in r/r T-ALL/LBL, with a a particular emphasis on its impact in patients with EMD.

The Value of Bone Marrow Assessment by FDG PET/CT, Biopsy and Aspirate in the Upfront Evaluation of Mantle Cell Lymphoma: A Nationwide Cohort Study.

Assessment of bone marrow infiltration (BMI) is part of the initial staging of mantle cell lymphoma (MCL), although BMI evaluated by biopsy (BMB) is not considered significant in the MIPI scales, and standardized recommendations remain lacking. To evaluate the accuracy and prognostic impact of BMI assessed by PET/CT and BMB in a large series of MCL patients. We deconstructed the IPI-NCCN, MIPI, and MIPI-c indices and considered BMI as positive if indicated by a BMB, PET/CT scan, or a combination of both. In the total cohort (n = 148), 110 patients had BMI detected by BMB and 33 by PET/CT. The sensitivity of BMB was higher than that of PET/CT (94.8% vs. 28.4%), as were its negative predictive value (84.2% vs. 27.8%) and accuracy (95.9% vs. 43.9%). In the total cohort, BMI detected by PET/CT showed a significant predictive value for PFS (p = 0.027), while BMB demonstrated independent prognostic value only in combination with PET/CT (p = 0.025). Among intensively treated patients (n = 128), PET/CT had significant clinical impact on PFS (p = 0.030), and when combined with BMB, it provided independent prognostic value for both PFS and OS (p = 0.026 and p = 0.033, respectively). Based on these findings, we propose a prognostic model (MCL-PET-I) that incorporates BMI by PET/CT, allowing for the identification of three groups with distinct clinical outcomes (p < 0.0001 for PFS and p = 0.00025 for OS). In the upfront work of MCL, PET/CT-based BMI has greater prognostic impact, while BMB remains essential for staging. We propose the MCL-PET-I prognostic index, which effectively differentiates between clinical risk groups.

Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) DLBCL with CAR T Cell Therapy: A Vodcast and Case Example.

Chimeric antigen receptor (CAR) T-celltherapy is effective in the treatment of patients with diffuse large B cell lymphoma (DLBCL), even those with high-grade disease. However, it has a unique safety profile, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and robust management of these events are important to maximize benefits. The aim of this vodcast is to outline the management of a patient receiving CAR T-cell therapy for relapsed/refractory (r/r) DLBCL. In January 2005, the patient was diagnosed with atypical chronic lymphocytic leukemia (CLL) and treated with two cycles of fludarabine and cyclophosphamide before stopping due to skin toxicity. In 2007, the patient progressed and received alemtuzumab. In January 2018, the patient was diagnosed with DLBCL (nongerminal center, stage IV-A, bone marrow infiltration); a clonality analysis with the previous CLL provided a negative result. In March 2018, the patient received first-line treatment with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP)) for six cycles. At this point, a positron emission tomography (PET) scan showed complete remission. Unfortunately, in December 2018, they experienced a relapse and second-line therapy with rituximab, etoposide, cytarabine, cisplatin, and prednisone (R-ESHAP) was started. Following the second cycle of R-ESHAP in February 2019, the patient progressed, and third-line treatment was provided by rituximab plus ifosfamide, gemcitabine, vinorelbine, and prednisone (R-IGEV) for four cycles. The last cycle of R-IGEV was received in May 2019, but the patient progressed. In July 2019, the patient received a tisagenlecleucel infusion. The authors describe the effectiveness of the CAR T-cell therapy and how the adverse events (AEs) encountered, including CRS and ICANS, were managed. Results from real-world evidence studies of tisagenlecleucel in DLBCL are similar to those observed in the pivotal clinical trials. In conclusion, CAR T-cell therapy can be effective and achieve long-lasting, durable responses in patients with high-risk r/r DLBCL. However, long-term follow up is key to watch out for late AEs and potential lymphoma relapse.

Preparing Nurses for CD20-CD3 Bispecific Antibody Treatment in Patients With Non-Hodgkin Lymphoma: A Scoping Review of Adverse Events and Management Strategies From Early Phase and Pivotal Trials.

Bispecific T-cell engaging antibodies (BsAbs) are novel agents used to treat B-cell non-Hodgkin lymphoma (B-NHL); these agents demonstrate a different toxicity profile compared with standard chemoimmunotherapy. To describe common adverse events (AEs) experienced by patients with B-NHL during BsAb treatment. MEDLINE, EMCARE, and EMBASE were searched for relevant studies. Prospective interventional clinical trials of CD20-CD3 BsAbs in late development reporting on safety data for B-NHL patients, published until March 2023, were included. This search identified 1481 records; 28 met the inclusion criteria. Cytokine release syndrome (CRS), neutropenia, pyrexia, and anemia were the most commonly reported AEs. CRS primarily occurred during the first cycle of treatment and was mostly low grade; 14 publications (48%) reported a grade ≥3; however, these occurred in less than 10% of patients. Mitigation strategies included premedication with corticosteroids, antipyretics, and antihistamines; step-up dosing; and planned hospitalizations. Two articles reported common signs and symptoms of CRS, which included pyrexia (98% and 99%), chills (13% and 35%), tachycardia (27% and 28%), and hypotension (24% and 38%). Supportive management, tocilizumab, and corticosteroids were widely used (reported in 16/28 studies) for the treatment of CRS. Patient risk factors for CRS included high tumor burden, bone marrow infiltration, and circulating disease. The AE profile of BsAbs requires specialized nurses, skilled in assessing patients for risk factors and recognizing signs and symptoms of AEs. Findings from this review will contribute to cancer nurses' knowledge of CD20-CD3 BsAbs for B-NHL, optimizing the quality and safety of patient care.

GLI3 Is Required for M2 Macrophage Polarization and M2-Mediated Waldenström Macroglobulinemia Growth and Survival.

Waldenstrom macroglobulinemia (WM) is a non-Hodgkin B-cell lymphoma, characterized by bone marrow infiltration with plasma cells and lymphocytes. The tumor microenvironment (TME) plays an important role in mediating WM cell biology, but the effects of macrophages on WM biology remains unclear. Here, we investigated the effects of macrophages on WM growth and survival and identified a novel role for transcription factor GLI3 in macrophage polarization. We found that co-culture of M0 and M2 macrophages promoted WM cell growth and survival, and co-culture WM cells with M0 macrophages induced M2-like phenotypes. Interestingly, GLI3 expression was induced in M2 macrophages (not M1), leading us to perform analysis of macrophages from mice lacking Gli3 in myeloid cells (M-Gli3-/- mice). A subset of differentially expressed genes implicated a role for GLI3 in macrophage polarization. Macrophages from M-Gli3-/- mice did not induce WM cell proliferation and reduced survival compared to M2 macrophages from WT mice. In addition, in vitro polarization of M0 macrophages from M-Gli3-/- was not able to induce M2 markers such as CD163, despite inducing iNos expression (M1 marker). Taken together, these results suggest a role for M2 macrophages in promoting WM cell growth and identify GLI3 as a modulator of macrophage polarization.

Development of ALL-Hematotox (ALL-HT): predicting post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia

Immune effector cell–associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. Although ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia (>14 days of absolute neutrophil count [ANC] <500/μl), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC <500/μl) was 13 days (95% confidence interval, 10-16 days), with 83 (53%) experiencing grade >3 ICAHT. Applying CAR-HT, nearly 90% were classified as high risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and postinfusion neutropenia (r = 0.64, P < .0001), we developed the ALL-Hematotox (ALL-HT) score, which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve = 0.84, P < .0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days; P < .0001), fewer rates of complete response (88% vs 98%; P = .03), and shorter median overall survival (9.8 vs 24 months; log-rank P = .0002). ALL-HT was also validated in 2 independent cohorts. The ALL-HT score refines a widely accepted predictive model of postinfusion hematotoxicity, applicable in B-ALL.

Nontuberculous Mycobacterial Infective Endocarditis: A Systematic Review of Clinical Characteristics and Outcomes.

Infective endocarditis (IE) due to nontuberculous mycobacteria (NTM) is a rare infection, and several outbreaks have been reported in the last 2 decades. However, the clinical spectrum is still poorly understood. This systematic review aimed to evaluate the clinical characteristics and outcomes in NTM IE. We searched the major electronic databases (PubMed, Scopus, and Google Scholar) with appropriate keywords to December 2023. We included studies based on predefined diagnostic criteria, and relevant data were collected on clinical presentation and treatment outcomes. The study was registered with PROSPERO (CRD42023492577). A total of 97 studies were reviewed, encompassing 167 patients with NTM IE. The earliest cases were reported in 1975, involving M chelonae and M fortuitum. M chimaera was the most prevalent species (38.9%), though rapidly growing NTM (RGM) were more common than slow-growing NTM (SGM; 59.3% vs 40.7%). Disseminated NTM infection occurred in 84% of cases, with bone marrow infiltration and osteomyelitis as frequent manifestations. Prosthetic valves were the main risk factor, present in 63.5% of cases. In native valve IE, nearly all cases (n = 27, 96%) were attributed to RGM. The overall mortality rate was 44.9%, with conservative management without surgery associated with poorer outcomes (66.7% vs 30.6%). Mortality was comparable between SGM and RGM IE, although relapses were more common in SGM IE (17.6% vs 1.9%). This review highlights the changing epidemiology of NTM IE with the emergence of RGM IE. Disseminated infections in the setting of prosthetic valves warrant NTM evaluation. The high mortality rate necessitates the role of early surgery.

Machine Learning Models Based on [18F]FDG PET Radiomics for Bone Marrow Assessment in Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is a heterogeneous group of cancers that triggers bone marrow infiltration in 20–40% of cases. Bone marrow biopsy in combination with a visual assessment of [18F]FDG PET/CT images is used to assess the marrow status. Despite the potential of both techniques, they still have limitations due to the subjectivity of visual assessment. The present study aims to develop models based on bone marrow uptake in [18F]FDG PET/CT images at the time of diagnosis to differentiate bone marrow status. For this purpose, a model trained for skeleton segmentation and based on the U-Net architecture is retrained for bone marrow segmentation from CT images. The mask obtained from this segmentation together with the [18F]FDG PET image is used to extract radiomics features with which 11 machine learning models for marrow status differentiation are trained. The segmentation model yields very satisfactory results with Jaccard and Dice index values of 0.933 and 0.964, respectively. As for the classification models, a maximum F1_score_weighted and F1_score_macro of 0.962 and 0.747, respectively, are achieved. This highlights the potential of these features for bone marrow assessment, laying the foundation for a new clinical decision support system.

Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry.

Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2-microglobulin ≥3 mg/L, and albumin <4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low-, intermediate-, and high-risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of MYD88 L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5-year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.

Isolated Bone Marrow Metastasis in Metastatic Carcinoma Breast: A Rare and Unique Case

Background Bone metastasis (BM) accounts for about 65%–75% of metastatic breast cancer (MBC) cases. Unlike BM, symptomatic bone marrow metastasis (BMM) is uncommon in MBC. The reported incidence of BMM is only 0.17% in MBC and 0.6%–1.7% in other solid tumours such as gastric and lung cancer. The extent of bone marrow infiltration leading to BMM manifestations is varied and complex. Diagnosis of BMM primarily relies on bone marrow aspiration smears and biopsies. The lack of specific clinical signs in BMM makes early diagnosis challenging, underscoring the need for expertise in this field. Due to limited data in this area, the appropriate treatment of breast cancer with BMM is not extensively discussed in significant guidelines. Most patients with BMM have hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) tumours. The goal is to improve understanding of this disease and provide effective diagnostic and treatment strategies.

Prevalence of Asymptomatic Changes in the Groin Region Among Adult Professional Soccer Players and Their Association With Limb Dominance.

To investigate the prevalence of asymptomatic radiologic groin region findings in adult professional soccer players using magnetic resonance imaging (MRI) and examine the influence of age and limb dominance on their occurrences. Cross-sectional trial. Soccer club medical service, private practice. Forty-seven male professional soccer players. Players underwent a groin presigning MRI scan with a magnetic field induction of 1.5 Tesla. Image analysis of their pubic bones was performed according to The Copenhagen Standardized MRI protocol to assess the pubic symphysis and adductor regions of players. The prevalence of various changes in the symphysis, pubic bone, and adjacent areas. Fifty images of pubic bones and adjacent regions (53.2%) highlighted 1 to 4 changes, while another 44 images (46.8%) demonstrated 5 or more changes. The most frequent changes observed in the pubic bone were joint surface irregularities (100%), symphyseal sclerosis (93.6%), pubic bone swelling (56.3%), parasymphyseal high-intensity line (55.3%), fatty infiltration in bone marrow (38.3%), and adductor tendinopathy (34%). When comparing the prevalence of different changes in the dominant and nondominant limbs, no statistically significant differences were found. In adult professional soccer players with no prior groin pain complaints in recent history (12 months), asymptomatic changes are extremely common in the pubic joint and adjacent areas, including those that are very likely to be considered the main cause of pain when investigated in soccer players with groin pain. None of these changes were associated with limb dominance.

Waldenstrom's Macroglobulinemia: A Case Report

Waldenström's macroglobulinemia (WM) is a rare, slow-growing hematologic malignancy marked by elevated levels of monoclonal immunoglobulin M (IgM) and bone marrow infiltration by lymphoplasmacytic cells. This case details a 72-year-old man who, during a pre-anesthetic consultation for lumbar spinal stenosis surgery, presented with neurological symptoms, fatigue, and headaches. Examination revealed pallor, and laboratory tests indicated anemia and an elevated erythrocyte sedimentation rate. Serum protein electrophoresis identified a monoclonal IgM spike, and bone marrow aspiration showed significant infiltration by small lymphoid cells, lymphoplasmacytoid cells, and plasma cells. WM was confirmed, and the patient was treated with dexamethasone, rituximab, and cyclophosphamide, with positive follow-up progress. This case underscores the importance of considering WM in the differential diagnosis for patients with unexplained anemia and elevated IgM levels, highlighting the need for timely diagnosis and treatment to manage potential complications.