Bone Marrow Biopsy Research Articles

Monoclonal gammopathy of clinical signifi cance with osteosclerotic lesions - a case report and a literature review.

Multiple myeloma is a common plasma cell neoplasia usually accompanied by the formation of osteolytic foci, whereas osteosclerotic myeloma is a very rare form of plasma cell dyscrasia. When osteosclerotic myeloma is detected, osteosclerotic foci are usually part of the POEMS syndrome. Osteosclerotic myeloma without other manifestations of the POEMS syndrome is an unusual finding. In a 46-year-old woman, osteosclerotic changes of the temporoparietal region caused soft tissue induration over this lesion, which initiated further investigation. Imaging studies subsequently showed multiple osteosclerotic foci in the skull. Examination of blood proteins revealed 8 g/L of IgG-lambda monoclonal immunoglobulin, subclass IgG1. In search of the cause of the osteosclerotic changes, FDG-PET/CT was performed, which revealed no FDG accumulation, i.e., no other tumor (breast or stomach cancer). Low-dose CT showed irregular bone structure, but not significant osteolytic or osteosclerotic foci. To map the extent of osteosclerotic changes, NaF-PET/CT imagination followed, which revealed multiple spots with high fluoride accumulation. A parietal bone biopsy showed osteosclerosis with minor clonal plasma cell infiltration. Trepanobioptic bone marrow sampling revealed an infiltration of bone marrow with atypical plasma cells in 8%. Flow-cytometric examination of bone marrow showed 0,37% of plasma cells, however predominantly (91%) clonal with lambda expression. MRI of the brain identified asymptomatic meningeal thickening. There was no evidence of POEMS syndrome in the patient; thus, we concluded the diagnosis as monoclonal gammopathy of clinical significance with osteosclerosis which was previously termed osteosclerotic multiple myeloma. Monoclonal gammopathy of clinical significance (MGCS) with osteosclerotic skeletal changes, documented on CT and multiple foci with intensive osteoneogenesis, documented on NaF-PET/CT without evidence of POEMS syndrome, is an extremely rare form of plasma cell dyscrasia. This publication documents the unique clinical manifestations of IgG-lambda type plasma cell proliferation without signs of POEMS syndrome and the role of NaF-PET/CT imaging. Classification of this disease as MGSC with osteosclerotic manifestations is more consistent with the indolent nature of the disease with a significantly better prognosis, compared with multiple myeloma.

Misleading Trails: Uncovering Systemic Mastocytosis Disguised as Eosinophilic Gastrointestinal Disorder - A Case Report

An uncommon class of illnesses known as mastocytosis is defined by aberrant mast cells in different tissues or organs. It encompasses mast cell sarcoma, systemic mastocytosis, and cutaneous mastocytosis. For those without advanced manifestations of the disease, the diagnosis of Systemic Mastocytosis can be protracted due to the high rate of symptom overlap with other illnesses. A 56-year-old female patient was brought to our department for a diagnosis because of her history of eosinophilia, chronic colitis, and skin allergies. The patient's eosinophilia remained in spite of treatment. The patient's blood count revealed persistent eosinophilia even after five months. An examination of the bone marrow aspirate showed a hypercellular bone marrow with a noticeable eosinophilic prominence. To our astonishment, the trephine biopsy showed sheets and nodules of mast cells, expressing strong positivity for CD117 immunostain. A review of the colonic biopsy also showed a significant mast cell presence as highlighted by CD117 immunostain. A definitive diagnosis of systemic mastocytosis was reached, indicating that, in situations of eosinophilia, a low index of suspicion and meticulous morphological examination are necessary to prevent delays in the diagnosis of mastocytosis, particularly in cases where there is no cutaneous involvement.

PANCYTOPENIA: Epidemiological and Etiological Profile in Adult Patients of the Internal Medicine Department, CHU Hassan II, Fès.

Introduction: Pancytopenia is a fairly common hematological condition encountered in routine clinical practice. Since there is a wide variation in the etiologies of pancytopenia, even in different populations of the same geographical region, the identification of underlying etiologies is important. With this in mind, our study was undertaken to investigate the epidemiological and clinico-hematological profile of pancytopenic adults with the aim of identifying the different etiologies of pancytopenia. Materials and Methods: This is a retrospective study including all adult patients with pancytopenia admitted to the internal medicine department at Hassan II University Hospital in Fez, Morocco, from January 1, 2019 to December 31, 2022. Pancytopenia is defined by the simultaneous presence of a hemoglobin level < 13.0g/dL in men and 12.0g/dL in women, a total leukocyte count < 4.0 × 10^9 /L and a platelet count < 150 ×10^9 /L. Each patient included in the study underwent a series of investigations, including: blood count and reticulocyte count; peripheral blood smear examination; vitamin assays; bone marrow aspiration; immunophenotyping; osteomedullary biopsy (OMB) and serologies. Patients already diagnosed and under treatment, as well as patients under 18 years of age, were excluded from the study. Results: A total of 164 patients with pancytopenia were identified during our study period. The mean age of our patients was 48 years [extremes 18y-89y], with a preponderance of women (87women/77men). Mucocutaneous pallor was present in 100% of our patients, hepatosplenomegaly in 22.56% and hemorrhagic syndrome in 18.29%. Infectious syndrome and bone pain were observed in 12 patients (7.31%) and 05 patients (3.04%) respectively. Nineteen (19) patients had microcytic anemia, 85 had normocytic anemia and 60 patients had macrocytosis. Vitamin assays revealed vitamin B12 deficiency in 43 patients (26.91%), while 15 patients (9%) had folate deficiency. Combined B12 and folate def

Effectiveness and Complications of Bone Marrow Aspirate Concentrate in Patients with Knee Osteoarthritis of Kellgren-Lawrence Grades II-III.

This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren-Lawrence (K-L) grades II-III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K-L grades II-III OA. The exclusion criteria were age of <40 years or >80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6-8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up (p < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 (p < 0.05) and from 68.4 to 83.3 points (p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K-L grades II-III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.

The effect of music on comfort, pain, and anxiety in patients with bone marrow aspiration and biopsy in Turkey: a mixed-methods study

AimThis study was conducted to determine the effect of music on the pain, anxiety, and comfort levels of patients who underwent bone marrow aspiration and biopsy.MethodsThis study was conducted on patients with hematological malignancies. Music was used with the intervention group. Patients’ pain, anxiety, and comfort levels were measured. In addition, qualitative data were obtained through in-depth interviews with patients.ResultsA significant difference (p < 0.05) was found between the experimental and control groups regarding pain, comfort and anxiety levels following the application of music. It was found that there was a negative correlation between comfort and pain (r=-0.442 p < 0.001) and between comfort and anxiety (r=-0.544 p < 0.001). As a result of qualitative interviews, patients mentioned the relaxing effect of music and the reduction of anxiety and pain levels. They also stated that music can be utilized as an alternative method.ConclusionAccording to the results of the present study, music reduced the pain and anxiety levels of the patients in bone marrow aspiration and biopsy and increased their comfort levels. We can say that music can be used in the clinic as a non-pharmacological method for pain, anxiety and comfort.Clinical Trials NumberNCT05895357 (Date:08/06/2023).

Heavy-chain deposition disease associated with multiple myeloma: a case report

Heavy-chain deposition disease (HCDD) is a rare disorder characterized by the deposition of monoclonal immunoglobulin. Due to the disease's rarity and diagnostic challenges, its prognosis is generally poor. Herein, we report a case of successful treatment of HCDD coexisting with multiple myeloma. A 56-year-old man presented at an outpatient clinic with complaints of whole-body pain, edema, and dyspnea that had persisted for 2 weeks. Diagnostic tests confirmed nephrotic syndrome, hematuria, and progressive renal failure. Serum immunofixation electrophoresis identified the presence of IgG kappa paraprotein. A diagnosis of multiple myeloma was established following a bone marrow biopsy. A renal biopsy revealed antibodies specific to the heavy chains of IgG on immunofluorescence, and electron microscopy showed diffuse electron-dense "powdery" densities in the glomerular basement membrane. Based on these findings, the patient was diagnosed with both HCDD and multiple myeloma. Following the diagnosis, the patient immediately began anti-plasma cell therapy using bortezomib, lenalidomide, and dexamethasone. Intermittent hemodialysis was initiated due to persistent azotemia during the diagnostic process; however, renal function improved significantly after only 1 month of therapy, allowing the discontinuation of dialysis. Early intervention with anti-plasma cell therapy, such as bortezomib, is known to improve prognosis in the early stages of the disease. This case report is presented to enhance understanding of HCDD and underscore the importance of prompt diagnosis and treatment in managing this rare condition.

Clinical clues for suspecting wild-type transthyretin cardiac amyloidosis in patients with monoclonal gammopathy of undetermined significance: a case report

BackgroundMyeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis.Case presentationA 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m2. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis.ConclusionsMGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.

REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina

AimsThe REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. MethodsREGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. ConclusionsThis is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Clinicopathological features and prognosis analysis of bone marrow biopsy involvement in 95 cases with mantle cell lymphoma

Clinicopathological features and prognosis analysis of bone marrow biopsy involvement in 95 cases with mantle cell lymphoma

POEMS syndrome with undetectable M-protein: a case report and literature review

BackgroundPolyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria.Case presentationWe report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone.ConclusionsMonoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren’t enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Vitality of autologous retromolar bone grafts for alveolar ridge augmentation after a 3-months healing period: A prospective histomorphometrical analysis.

The incorporation of retromolar bone grafts used for alveolar ridge augmentation is not well understood. This prospective observational study aims to supply histomorphometrical data from bone graft biopsies taken at the time of retrieval and after a 3-month healing period using patient-matched biopsies. In 17 patients, trephine biopsies of the graft were acquired at the time of graft retrieval and after a 3-month healing period. The biopsies were compared histomorphometrically regarding the number of osteocytes, appearance of osteocyte lacunae, quantity, surface area, and activity of the Haversian canals. All grafts appeared clinically stable after screw removal and 17 implants were placed. Histomorphometric analysis revealed no significant difference in the number of osteocytes (p = .413), osteocyte lacunae (p = .611), the ratio of filled/empty osteocyte lacunae (p = .467) and active Haversian canals (p = .495) between the biopsies retrieved after a 3-months healing period with those at the time of grafting. The only significant difference was noted in the mean surface area of the Haversian canals (p = .002). Specifically, the grafts post 3-month healing showed a significantly larger mean area (0.069 mm2) compared to the time of grafting (0.029 mm2). This study demonstrates, compared to other data, a high rate of vital structures in retromolar bone block grafts after 3 months of healing, exhibiting the same histological features in comparison to the biopsies from the native alveolar ridge. Standard histomorphometrical parameters, e.g., the amount of filled or empty osteocyte lacunae for the description of the vitality of the graft need to be reappraised.

Transient Abnormal Myelopoiesis in Down Syndrome Patients

Neonates with Down Syndrome (DS) have a propensity to develop the unique myeloproliferative disorder, Transient Abnormal Myelopoiesis (TAM). Transient abnormal myelopoiesis usually resolves spontaneously in &lt; 3 months, but approximately 10% of patients with TAM die from hepatic or multi-organ failure. After remission, 20% of patients with TAM progress into acute myeloid leukemia associated with down syndrome (ML-DS). The patient was a full-term 2-day-old baby girl with a birth weight of 3300 gr. Physical examination revealed dysmorphic facial features, hypertelorism, macroglossia, and low set ears, which is a characteristic sign of DS face, skin rash, and there was no anus. On examination of peripheral blood smears and bone marrow aspiration, hematological abnormalities, and circulating blast cells were found. Early diagnosis of low-lying anorectal malformation (MAR) without fistula and down syndrome. In treating patients with TAM, it is first necessary to know whether they have trisomy 21 syndrome, then trace the existing hematological disorders to find the GATA 1 genetic mutation. The most crucial hematological problem in patients with DS is leukemia. Mutations in the GATA 1 gene and the presence of DS can result in abnormal proliferation of megakaryocytes and erythroid progenitors in the fetus and hematological abnormalities in TAM. Transient abnormal myelopoiesis can be fatal in up to 10% of patients and resolves spontaneously. Therefore, laboratory examinations are very significant, including blood tests, peripheral blood smears, supporting examinations such as bone marrow aspiration, monitoring of clinical symptoms, and close monitoring of comorbidities. Examination repeat or follow-up bone marrow aspiration is required within six months of patient follow-up to reduce the risk of further complications. In this case, a follow-up examination is highly recommended because if there are no changes, the further examination must be carried out.

Acute Erythroid Leukemia: From Molecular Biology to Clinical Outcomes.

Acute Erythroid Leukemia (AEL) is a rare and aggressive subtype of Acute Myeloid Leukemia (AML). In 2022, the World Health Organization (WHO) defined AEL as a biopsy with ≥30% proerythroblasts and erythroid precursors that account for ≥80% of cellularity. The International Consensus Classification refers to this neoplasm as "AML with mutated TP53". Classification entails ≥20% blasts in blood or bone marrow biopsy and a somatic TP53 mutation (VAF > 10%). This type of leukemia is typically associated with biallelic TP53 mutations and a complex karyotype, specifically 5q and 7q deletions. Transgenic mouse models have implicated several molecules in the pathogenesis of AEL, including transcriptional master regulator GATA1 (involved in erythroid differentiation), master oncogenes, and CDX4. Recent studies have also characterized AEL by epigenetic regulator mutations and transcriptome subgroups. AEL patients have overall poor clinical outcomes, mostly related to their poor response to the standard therapies, which include hypomethylating agents and intensive chemotherapy. Allogeneic bone marrow transplantation (AlloBMT) is the only potentially curative approach but requires deep remission, which is very challenging for these patients. Age, AlloBMT, and a history of antecedent myeloid neoplasms further affect the outcomes of these patients. In this review, we will summarize the diagnostic criteria of AEL, review the current insights into the biology of AEL, and describe the treatment options and outcomes of patients with this disease.

Increased Cellular Dosage of Bone Marrow Aspiration Concentrate Does Not Translate to Increased Clinical Effectiveness in Knee Osteoarthritis: A Phase I Dose Escalation Study.

Knee osteoarthritis (KOA), a chronic degenerative disease, significantly impairs quality of life due to pain and mobility limitations. Traditional treatments focus on symptom management without addressing the underlying disease progression, leading to a growing interest in regenerative medicine approaches. Bone marrow aspirate concentrate (BMAC), rich in mesenchymal stem cells and growth factors, has shown potential for cartilage repair and symptom relief in KOA. Despite promising outcomes, the optimal BMAC dosage for knee OA treatment remains undetermined. This study aims to evaluate the clinical efficacy and safety of varying BMAC dosages in knee OA treatment. This prospective controlled dose-escalation study involved 75 patients with early-stage knee OA, categorized into three groups based on BMAC dosage administered 10 × 106 cells (low-dose group), 50 × 106 cells (medium-dose group), or 100 × 106 cells (high-dose group). All the patients underwent a single intra-articular injection of BMAC and were monitored over a year. The primary outcomes include Visual Analog Scale (VAS) for pain and the Knee Injury and Osteoarthritis Outcome Score (KOOS) for joint function recorded at baseline, 1, 3, 6, and 12months post-intervention. Adverse events were also documented. Significant clinical improvements in VAS and KOOS scores were noted across all groups at all time points compared to the baseline. However, these improvements did not significantly differ between dosage groups throughout the follow-up period. Adverse effects were minimal and primarily consisted of transient post-injection pain and effusion, with no dose-dependent increase in complications. BMAC treatment for knee OA is safe and demonstrates potential for significant pain relief and functional improvement, irrespective of the dosage administered within the tested range. The lack of significant differences among varying dosages suggests a plateau in therapeutic efficacy beyond a certain threshold. Further research is necessary on the long-term outcomes to optimize the dosing strategy.

Flow Cytometry-Based Detection of Minimal/Measurable Residual Disease Predicts Survival Outcomes in Pediatrics, Adolescents, and Young Adults With T-acute Lymphoblastic Leukemia.

Measurable/minimal residual disease (MRD) is considered the single most powerful high-risk factor in acute leukemia, including T-cell acute lymphoblastic leukemia (T-ALL). In this study, we evaluated the impact of flow cytometry (FC)-based detection of MRD on survival outcomes in pediatrics, adolescents, and young adults (AYA) with T-ALL. We included 139 patients, 88 pediatric patients between the ages of one and 14 years, and 51 AYA patients between 15 and 39 years of age, over a period of three years and were treated with the Indian Collaborative Childhood Leukemia Group (ICiCLe) protocol. MRD assessment was performed on post-induction (PI) bone marrow aspirate samples using a 10-color 11-antibody MRD panel on a Gallios instrument (Beckman Coulter, Miami, FL, USA). MRD value > 0.01% was considered positive. PI-MRD status was available in 131 patients. The five-year event-free survival (5-year EFS) in PI-MRD positive patients was inferior to those of negative patients (13.56% vs 79.06%), which was statistically significant (P < 0.001). However, the five-year overall survival (5-year OS) did not show any statistically significant difference between PI-MRD positive and negative T-ALL patients (92.93% vs 94.28%). The hazard ratio (HR) for 5-year EFS and MRD positivity was 8.03 (p-value < 0.0001). HR for 5-year EFS and early T-cell precursor ALL (ETP-ALL) was 2.63 (p = -0.02). PI-MRD detected using FC is a strong predictive factor of inferior survival outcomes in pediatrics, AYA patients with T-ALL. PI-MRD positivity can be used to modify the treatment of T-ALL patients, especially in resource-constrained developing countries where molecular tests are not widely available.

Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study.

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.

Hemophagocytic Lymphohistiocytosis: A Case Series From a Tertiary State Hospital in Malaysia and a Review of Current Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a lethal emergency. Delaysin diagnosis and treatment are detrimental to the health of patients. Classical clinical manifestations of HLH include fever, cytopenia, liver dysfunction, central nervous system involvement, and coagulopathy. We report seven cases of secondary HLH in adults diagnosed from a total of 1200 bone marrow aspiration and trephine biopsy (BMAT) examinations in our center, with various presentations and underlying triggers including infection, malignancy, and autoimmune disease. HLH can present with non-specific signs and symptoms. Early recognition of HLH is crucial to enable the commencement of therapy as early as possible to prevent mortality resulting from multi-organ failure.

BLASTING BMAC: A NOVEL THERAPY TO IMPROVE HEALING IN FUSION SURGERY

IntroductionFusion represents an effective treatment option in patients affected by end-stage arthritis. To minimise the risk of non-union following fusion, biological preparations such as bone marrow aspirate concentrate (BMAC) are commonly used intra-operatively. Mechanotransduction represents an emerging field of research whereby physical stimuli can be used to modulate the behaviour and differentiation of cells. Blast waves (a subtype of shock waves) are one such physical stimulus. The aim of this study was to investigate whether the osteogenic potential of BMAC can be enhanced using a blast wave, and thus improve its efficacy in fusion surgery.MethodsHuman BMAC samples were obtained from three healthy patients and exposed to a single blast wave (peak overpressure= 50psi), before being placed in a suspension of mesenchymal stem cells, to represent the biological environment of the fusion site. Three test groups were used: MSC (the experimental control); MSC + BMAC; MSC + BMAC + blast wave. Calcium mineralisation assays were performed on the MSCs on Day 7 and 14 to assess for osteoblastic transformation.ResultsCalcium mineralisation on Day 7 was significantly increased in the MSC + BMAC group compared to the MSC group (mean percentage change 42.12 vs 0.0, p=0.012). The MSC + BMAC + blast wave group also demonstrated significantly increased levels compared to the MSC + BMAC group (84.56 vs. 42.14, p = 0.039). The difference in calcium mineralisation between the MSC and MSC + BMAC + blast wave groups was strongly significant (0.00 vs. 84.56, p = 0.003).ConclusionExposure of BMAC to a single blast wave enhances its osteogenic potential. This represents a potential novel way to improve healing following fusion surgery and reduce the rates of non-union.

Practice makes perfect: Using simulation to build and assess competency in bone marrow biopsy for heme/onc fellows.

9042 Background: The American Board of Internal Medicine (ABIM) requires that Hematology/Oncology fellows demonstrate competence in bone marrow biopsies (BMB). However, offers no guidance in assessment methods. Neither the "see one, do one, teach one" nor the "complete 5 procedures" approach is sufficient to ensure competency. As this is a potentially painful procedure that requires knowledge of landmarks, simulation in a safe environment is an ideal way to introduce BMB to trainees. In 2015, we started a simulation program to teach fellows how to perform BMB using a cadaver pelvis, and assess their BMB competency. Methods: The Hematology Oncology Fellowship Program at Gundersen Health System holds a half-day simulation for our 6 fellows each July. We begin with a self-evaluation of current skills, using an 8-question pre-test. We then view a demonstration video, pausing to discuss key learning points. Fellows are given a detailed check list of the steps of the procedure. They then experiment with the tools of the procedure and practice sterile technique. We discuss the indications, contraindications, consent, and the procedure itself. For part two, fellows are divided into two groups, each consisting of a first year (F1), second year (F2), and third year (F3) fellow. A cadaver pelvis is used as the model and is positioned in a prone position. Each team is assigned a side of the pelvis. The F3 demonstrates the procedure from start to finish while the F2 and staff assesses competency and the F1 follows with the procedure check list. Once the F3 has completed the procedure and is deemed "competent" they become the leader of the session for their team. F1s can practice as many times as desired, under the guidance of the F2 and F3. F2s also have a chance to refine their skills. After the simulation is complete, fellows repeat the self-evaluation, and we debrief. Results: 44 fellows completed the simulation (F1=16, F2=14, F3=14). Questions for the pre- and post-tests were ranked on a 5-point Likert Scale of strongly agree (1) to strongly disagree (5). F1s had the worst self-assessment prior to the procedure, with a mean score of 2.4 for all questions. However, their post-test self-assessment improved to 1.6. F2s started at 1.5 and improved to 1.1 after the simulation. F3s started at 1.2 and improved to 1.0. All fellows answered that this was a useful exercise and should be continued. Comments were consistently positive, speaking to the importance of a check list, the relaxed atmosphere, and having senior fellows teach the junior fellows. Conclusions: BMB simulation allows for a low-stakes introduction to a stressful procedure, while promoting a team approach to learning. It also gives an opportunity to verify competence for graduating fellows. Fellows self-reported improvement following the session as well as from year to year. Fellows value this learning experience and look forward to it each year.

Improving adequacy rates of bone marrow aspirate and core biopsies through training and a bedside X-ray device.

e23228 Background: Bone marrow (BM) evaluation is crucial to the diagnosis of hematolymphoid disorders. WHO requires an adequate number of well-spread-out spicules in aspirates and defines an adequate BM core biopsy as ≥1.5 cm with at least 10 inter-trabecular areas (ITA). Gross examination of the core biopsy at the bedside can be misleading due to attached clot, thick periosteum, and cortical bone, or tangential biopsies, which histologically results in biopsy without adequate ITAs. Suboptimal BM biopsies hinder appropriate diagnosis, delay patient care, and may require the patient to undergo additional BM biopsies. Bedside image analysis via a cabinet x-ray system can be utilized as a point-of-care tool to assess the amount of evaluable marrow permitting re-biopsy at the time of the procedure. Methods: The study was conducted over 5 months at Westchester Medical Center. We retrospectively estimated BM adequacy rates by analyzing the aspirate quality and measuring the BM core biopsy length. Subsequently, a training demonstration to the proceduralist (fellows in training) by an experienced attending was performed and the adequacy rates were reassessed. BM biopsies were analyzed with a cabinet x-ray system, Faxitron, soon after biopsy, then subjected to routine histology and processing. High-resolution images of the core biopsy were obtained. The length of the core biopsy and the number of ITAs were calculated from the x-ray images. Measurement of the gross biopsy length and microscopic assessment of evaluable marrow were compared to the measurements obtained by x-ray imaging. Results: Our adequacy rates which met aspirate quality were 5% (1/20) pre-intervention and 65% (13/20) post-intervention. The aspirate smear quality improved after the demonstration technique to 65%. Only 13/53 core biopsies exceeded the WHO standard of 1.5 cm by microscopy, while 34/53 were grossly estimated to be &gt; 1.5 cm. There was general concordance between the number of ITAs and the length of core biopsies by microscopy. In approximately 20% of cases, the x-ray images highlighted suboptimal core biopsy ( &lt; 10 ITA/cortical bone/cartilage), which weren’t apparent by gross examination alone at the bedside. Utilizing x-ray image measurements, core biopsy fragment length was shown to be in concordance with microscopic estimation of length and number of ITAs. X-ray imaging readily identified clot sections (non-radiopaque), sclerotic cortical bone (absence of trabeculae), and periosteum (soft tissue shadow) in all 10 sub-1 cm biopsies. Conclusions: We conclude that a standard instruction technique of slide preparation can improve the quality of bone marrow aspirate. Core biopsy length and number of ITAs can easily be estimated using bedside point-of-care x-ray analysis to ensure adequate BM evaluations. We propose training and the routine use of bedside x-ray machine to improve the adequacy rates of BM biopsies.