Search Results (192)

Knee osteoarthritis (OA) is a whole-joint disease involving subchondral bone lesion (BML) that predict treatment outcomes. This retrospective, non-randomized study compared extracorporeal shockwave therapy alone (ESWT), autologous protein solution and ESWT (APS), intra-articular mesenchymal stromal cell and ESWT (MSC-A), and combined intra-articular and intra-osseous MSC and ESWT (MSC-B) for knee OA with BML. We hypothesized that combination therapies would provide superior and earlier outcomes for advanced cases. The primary outcome was the change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 3 and 6 months. The results showed ESWT was effective, but only in the absence of articular surface collapse (KOOS IV (pre–6M) = 18.6 ± 13.9) vs. presence of collapse (4.4 ± 6.5). APS led to earlier improvement in cases without subchondral bone plate (SBP) tear (KOOS IV (pre–3M) = 18.4 ± 12.7) vs. ESWT 12.0 ± 14.0). MSC-A with SBP tear achieved significant early gain (KOOS IV (pre–3M) = 13.9 ± 10.1) but plateaued by 6 months. MSC-B without collapse showed significant 6-month improvement (KOOS IV (pre–6M) = 15.8 ± 8.6), but failed in collapse cases (KOOS IV (pre–6M) = −4.4 ± 7.7). ESWT is effective, APS provides early benefits, and MSC-B is promising for advanced SBP tear cases, but articular surface collapse limits efficacy across all therapies. Full article

Background: Ectopic bone formation models provide useful insights into bone tissue formation and remodeling processes. The use of a subcutaneous site emphasizes the focus on cytokine signaling and cell migration and proliferation while minimizing the effect of mechanical loading and direct interaction with surrounding stem cells. Methods: To study the effect of BMP3 on bone formation and remodeling, Bmp3^-/- mice were subcutaneously implanted with an autologous blood coagulum device containing BMP6, and bone formation was examined at days 7 and 14 post-implantation. Bone marrow cell composition was assessed using FACS. Formation of ectopic bone was analyzed using micro-CT, immunohistochemistry, and RNAseq to obtain transcriptomic data. Results: Bone marrow from Bmp3^-/- mice showed reduced lymphoid-lineage subsets, expanded myeloid lineage, and altered proportions of several osteochondroprogenitor subsets. A limited amount of newly formed bone tissue was seen in the implants after 7 days, while ectopic bone was more evident after 14 days, with significantly more bone in the Bmp3^-/- mice compared to WT mice. Localization of Sox9 and Runx2 showed a more advanced stage of bone tissue remodeling in Bmp3^-/- mice. Transcriptomic analysis showed upregulation of approximately 1700 genes on day 7 and 190 genes on day 14. Conclusions: These results suggest that BMP3 regulates the composition of bone and cartilage progenitor populations in bone marrow and consequently bone formation by arresting the remodeling of cartilage to bone tissue. The lack of BMP3 in ectopic bone accelerates the transition from the cartilaginous template to proper bone tissue. Full article

Multiple myeloma (MM) is one of the most common hematological malignancies and remains incurable. However, the survival of multiple myeloma patients has significantly increased due to the implementation of novel therapies along with autologous stem cell transplantation, changing the natural history of the disease. Consequently, there is an unmet need for more sensitive response assessment techniques capable of quantifying minimal tumor burden to identify patients at higher risk of early relapse. Multiparameter flow cytometry (MFC) is an essential tool for diagnosing and monitoring patients with various hematological conditions and has recently gained prominence in identifying, characterizing, and monitoring malignant plasma cells. The implementation of Next-Generation Flow (NGF) by EuroFlow aims to overcome the pitfalls of conventional MFC, including lack of standardization and lower sensitivity, by offering standardized and optimized protocols for evaluating response depth. Both MFC and NGF have wide-ranging applications in MM for diagnosis and measurable residual disease (MRD) monitoring. Plasma cell identification and clonality evaluation through MFC and NGF assist in diagnostic workup and are routinely used to assess therapeutic response through MRD analysis. Additionally, flow cytometry is applied for circulating tumor plasma cell (CTPC) enumeration, which has demonstrated significant prognostic value. Immune composition studies through MFC may provide better understanding of disease biology. Furthermore, MFC provides additional information about other bone marrow cell populations, assessing cellularity, immunophenotypic characteristics of plasma cells, and possible hemodilution. This review explores the applications of MFC and NGF in MM, highlighting their roles in diagnosis, response assessment, and prognosis. Beyond their established use in MRD monitoring, flow cytometry-derived immunophenotypic profiles show strong potential as cost-effective prognostic tools. We advocate for future studies to validate and integrate these markers into risk stratification models, complementing cytogenetic analyses and guiding individualized treatment strategies. Full article

Background: Sarcina ventriculi is a bacterium predominantly reported in the stomach and associated with emphysematous gastritis, delayed gastric emptying, gastroparesis, or gastric outlet obstruction. Its prevalence is increasing among patients with a history of organ transplants, immunosuppression, and graft-versus-host disease (GVHD). This bacterium can be detected on histology with characteristic tetrad packet morphology; however, confirmation requires PCR and molecular studies. The role of Sarcina ventriculi in human diseases is not fully understood and has unclear clinical significance. While certain studies point to a possible pathogenic role, others regard its detection as incidental with no clear clinical consequence. Case presentation: Herein, we report a case of a 39-year-old male patient with primary refractory cHL, stage IVb, who underwent an autologous bone marrow transplant (BMT) and an allogeneic stem cell infusion. His post-transplant course was complicated by chronic kidney disease (CKD), malnutrition, depression, myopathy, skin, and colon GVHD. He eventually developed sepsis, was admitted to the ICU and developed multiorgan failure and passed away. The patient developed diarrhea, and the gastrointestinal specialist was consulted and revealed ulcerated ileitis and colitis. Biopsies were taken to evaluate for CMV infection and GVHD. The terminal ileum biopsy mainly revealed ulceration with granulation tissue formation and abundant microorganisms arranged in distinctive tetrads, characteristic of Sarcina ventriculi. The colonic biopsies were consistent with GVHD grade II. Conclusions: The significance of Sarcina microorganisms and their mechanisms of injury remain poorly understood. The identification of Sarcina ventriculi in the terminal ileum, which is an unusual and previously unreported finding, adds a new perspective to our understanding of its pathogenic potential and anatomical distribution. While the patient’s clinical decline was influenced by multiple factors, including GVHD, recurrent sepsis, and multiorgan failure, the role of Sarcina ventriculi as a potential exacerbating factor remains unclear. Full article

Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safety, tolerability, and clinical activity of MDG1011 in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). Methods: Nine of thirteen enrolled patients received MDG1011 at dose levels ranging from 0.1 to 5 × 10⁶ TCR-T cells per kg body weight. In addition to clinical assessments, immune monitoring of cytokines associated with cytokine release syndrome (CRS), presence and persistence of MDG1011, and changes in levels of PRAME mRNA were used to assess safety and potential biological activity at defined time points. Results: The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression. Various parameters, such as measurable clinical responses in two patients, the occurrence of CRS in two additional patients, and reductions in PRAME mRNA levels in bone marrow (BM) or peripheral blood (PB) in seven patients, served as signs of the clinical and biological activity of MDG1011 TCR-T therapy. Conclusions: Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden. Full article

Concentrated growth factor (CGF) is an autologous blood-derived product widely used in regenerative medicine due to its high concentration of growth factors and platelets. In this study, the ability of primary stem cells isolated from human CGF to differentiate into adipocytes, endothelial cells, and neuronal-like cells was evaluated in vitro. CGF primary cells (CPCs) were obtained from CGF fragments and characterized after one month in culture. These cells were positive for the surface markers CD105, CD45, CD31, and CD14, and also expressed mRNA levels of the stemness markers Nanog and Oct3/4 comparable to human bone marrow mesenchymal stem cells (BMSCs). Results showed that, following appropriate differentiation protocols, CPCs, similarly to BMSCs, were able to differentiate into adipogenic, endothelial, and neuronal lineages, acquiring specific phenotypic and molecular markers. Adipogenic induction resulted in lipid accumulation and the upregulation of key genes, including PLIN2, FABP4, CD36, and FASN. Under pro-endothelial conditions, the cells exhibited increased expression of endothelial markers, eNOS, VEGFR-2, and CD31. Neuronal induction promoted the expression of β-tubulin III, Nestin, and Neurofilament. Overall, this work highlights the remarkable plasticity of CPCs and supports their potential application in multilineage regenerative therapies. Full article

Half of all Canadians will develop cancer at some point in their lifetimes. These rates have increased substantially over the last decade alongside increasing effectiveness and complexity of treatment options. Therefore, the need for patients to receive both an early diagnosis and ongoing care has never been so important. In Alberta, referrals to oncology specialty care have increased 18% in the last 7 years with no commensurate increase in the number of oncology health care professionals. Challenges with oncologic care access and provider recruitment are not unique to Alberta. In 2004, Cancer Care Alberta, specifically the Cross Cancer Institute (CCI), embarked on an initiative focusing on nurse practitioner (NP) care provision, aiming to address these gaps. The purpose of this article is a description of four distinct NP care models: the Assigned model, Consultative model, Partner model, and Most Responsible Provider (MRP model) significantly contributing to enhanced and expanded cancer care delivery at CCI. To the best of our knowledge, we are the first to demonstrate how NPs can significantly address the rapidly expanding demands for specialist oncology care. This work highlights roles and exemplars of NP care to meet the evolving needs of cancer patients, the multidisciplinary care team and the health system. Full article

Introduction: Despite the approval of novel agents that have significantly improved long-term survival rates for multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), most patients eventually relapse. The failure to achieve or maintain bone marrow (BM) minimal residual disease (MRD) negativity is a recognised adverse prognostic factor for progression-free survival (PFS) and overall survival (OS). Contamination of stem cell apheresis by clonal plasma cells may also affect prognosis, though data remain limited. Methods: We conducted a prospective, single-centre observational study including 100 newly diagnosed MM patients eligible for ASCT and treated with bortezomib-based triplet induction. MRD was assessed both on BM and apheresis samples using multiparameter flow cytometry (MFC-MRD) with a sensitivity of 10⁻⁵. Results: Clonal plasma cells were detected in 22 apheresis samples (aMRD+), all of which were associated with BM MRD positivity. Patients with aMRD+ had inferior pre-ASCT responses (≥VGPR: 10% vs. 63%, p = 0.005) and worse post-ASCT BM MRD negativity rates (4% vs. 49%, p = 0.048). After a median follow-up of 52.4 months, aMRD+ was associated with shorter progression-free survival (median 38.5 vs. not reached, p = 0.007) and overall survival (median 60 months vs. not reached, p = 0.003). Conclusions: Contamination of the apheresis product is associated with persistent BM disease and poorer outcomes. Combined MRD assessment in both bone marrow and apheresis may improve risk stratification in MM patients undergoing ASCT. Full article

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: Interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) are believed to possess a role in the pathophysiology of multiple myeloma (MM). We aimed to assess the significance of these parameters in the diagnosis, monitoring, and prognosis of the disease by examining them in patients at diagnosis and post-treatment and comparing the findings with those of healthy individuals. Methods: We conducted blood sampling from 35 patients diagnosed with MM at the time of diagnosis and from 15 of these patients post-treatment. We additionally assessed similar serum markers in a control group of 15 healthy individuals. Furthermore, we documented laboratory results, organ involvement, comorbidities, and CD27-CD81 levels assessed using flow cytometry in the bone marrow, along with treatments and patient responses. We also examined the quantity of cells collected during mobilization in patients who had autologous stem cell transplantation. Results: We found a positive correlation (p = 0.028/p = 0.035) between IL-10 and VEGF with the international staging score. In patients with renal involvement, IL-10 levels were higher and VEGF levels were lower than those without renal involvement (p = 0.011/p = 0.012). We showed that VEGF levels decreased significantly with treatment (p = 0.001). We found no statistically significant correlation between treatment responses and IL-10 and VEGF. The number of CD34 cells collected by mobilization showed a negative correlation with CD27 and a positive correlation with VEGF (p = 0.007/p = 0.032). Conclusions: Serum IL-10 level is associated with ISS and renal involvement in MM patients. There is a positive correlation between serum VEGF levels and the number of stem cells collected during mobilization. As CD27 expression increases, the number of stem cells collected in mobilization decreases. Full article

Humanized mice generated by hematopoietic stem cell (HSC) transplantation are limited by the immune system developed being allogeneic to the tumor. We have innovated a platform to reconstitute an autologous human immune system (HIS) in immunodeficient NOG-EXL mice from mobilized peripheral blood (MPB)-CD34 cells, along with PDX generated from the same patient’s tumor tissue. Patients consented under an IRB-approved protocol for tumor biopsy and HSC apheresis at Emory University. HSC collection included mobilization with G-CSF and plerixafor, immunomagnetic bead isolation with CliniMACS, and cryopreservation of CD34⁺ cells. PDX were established from biopsies or surgical specimens by passaging into immunodeficient mice. Irradiated NOG-EXL mice were engrafted with HSCs by intravenous transplantation of CD34⁺ HSC. Engraftment of human T cells, B cells, and myeloid cells in peripheral blood was assessed by serial flow cytometry of blood samples, with final assessment of immune components in spleen and bone marrow at 30 weeks. Twenty-eight PDX models were generated from 43 patients with HNSCC; 1 patient underwent apheresis. HSC engraftment in blood was observed in 100% of NOG-EXL mice at 8 weeks post-transplant, with 5–20% hCD45⁺ cells present in the periphery. B-cell development was predominant at early time points and declined over time. Human T-cell and subset development of CD4⁺ and CD8⁺ T cells were observed in blood from 15 weeks post-transplant. Strong development of the myeloid lineage (CD33⁺) was observed starting at 8 weeks and persisted throughout the study. These data demonstrate that mobilization and apheresis of HNSCC patients is technically and clinically feasible and may allow the establishment of autologous HIS-PDX mice. Full article

Introduction: Multiple myeloma constitutes approximately 12% of hematologic malignancies and predominantly affects older adults, significantly compromising their quality of life. Although exercise interventions have shown benefits in oncology, evidence specific to MM remains limited and of low certainty. The presence of complex comorbidities in MM patients necessitates highly individualized approaches. Prehabilitation has emerged as a promising strategy to enhance functional capacity prior to autologous stem cell transplantation. This case study evaluates the feasibility of a personalized, scheduled exercise intervention delivered via telerehabilitation. Intervention: This case study seeks to examine the feasibility of implementing a personalized and scheduled exercise intervention within a telerehabilitation framework for a medically complex patient with multiple myeloma (MM). The 12-week prehabilitation protocol is designed to enhance physical function prior to autologous bone marrow transplantation by integrating therapeutic exercise targeting key parameters related to quality of life and clinical resilience, such as muscular strength, aerobic capacity, coordination, and overall well-being. The intervention includes concurrent training (strength and aerobic exercises) delivered 2–3 times per week, with aerobic activities conducted independently at home through a virtual format. Assessments were performed at baseline and post-intervention. Results and conclusion: A personalized exercise program, implemented through a hybrid model of in-person and telerehabilitation, is both feasible and safe. It has the potential to enhance physical function and quality of life in patients with multiple myeloma. Further research is necessary to validate these findings across broader patient populations. 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

Background/Objectives: Multiple myeloma is a malignancy of plasma cells detected in the bone marrow, inducing symptoms like anemia, hypercalcemia, renal problems, and bone fractures in multiple myeloma patients, affecting their quality of life. The bone marrow microenvironment plays a crucial role in the prognosis and progression of the disease. The purpose of this study was to examine the relationship between the percentages of the major cell populations of the bone marrow, including immune cells, and physical function/quality of life in multiple myeloma patients after first-line treatment. Methods: Twenty-one multiple myeloma patients (N = 14 men, N = 7 women) participated in the study after completing first-line treatment. Bone marrow and blood samples were taken one hundred days after transplantation, while physical function (6 min walking test, handgrip test, maximal aerobic power, and isometric strength), health-related quality of life (QLQ-C30), and body composition (DXA) were assessed 2–5 days later. Flow cytometry was used to assess the percentages of plasma cells, mast cells, B cells (total, precursors, naïve, and memory), T cells (total, CD27− and CD27+), NK/NKT cells (total, CD27− and CD27+), eosinophils, monocytes, neutrophils, myeloid progenitors, erythroblasts, and erythroid progenitors, expressed as percentages of total nucleated cells of the bone marrow. Results: The percentage of CD27+ NK/NKT cells was correlated with five parameters of the quality of life questionnaire: physical function (r = 0.78, p = 0.005), role functioning (r = 0.69, p = 0.020), fatigue (r = −0.86, p = 0.000), pain (r = 0.68, p = 0.021), and dyspnea (r = −0.80, p = 0.003). Conclusions: In conclusion, stronger immune surveillance in the bone marrow from CD27+ NK/NKT cells is correlated with better quality of life in multiple myeloma patients. Full article