Resveratrol Alleviates Osteoporosis by Promoting Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via SITR1/PI3K/AKT Pathway / El Resveratrol Alivia la Osteoporosis al Promover la Diferenciación Osteogénica de las Células Madre Mesenquimales de la Médula Ósea a Través de la Vía SITR1/PI3K/AKT

SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

Common mental disorders in hematopoietic stem cell transplant patients: a scoping review / Trastornos mentales comunes en pacientes con trasplante de células madre hematopoyéticas: revisión del alcance / Transtornos mentais comuns em pacientes transplantados com células-tronco hematopoéticas: revisão de escopo

ABSTRACT Objective: to map common recurrent mental disorders in patients undergoing hematopoietic stem cell transplantation. Methods: this is a scoping review carried out in January 2022 in electronic databases and repositories of dissertations and thesis. Studies that answered the research question, met the objective of the study and were available in full electronically, in any language, were included. Results: the sample consisted of 28 studies, 14 of which were published in the United States of America. The common mental disorders found were depressive, anxiety, post-traumatic stress and mood disorders. Twenty symptoms were mentioned, among the most prevalent are fatigue and sleep disorders/insomnia. Conclusions: the difficulty and importance of carrying out the differential diagnosis of these disorders were highlighted, since their symptoms can be confused with other health problems and have a strong potential to interfere with patients' evolution.

RESUMEN Objetivo: mapear los trastornos mentales recurrentes comunes en pacientes sometidos a trasplante de células madre hematopoyéticas. Métodos: se trata de una revisión de alcance realizada en enero de 2022 en bases de datos electrónicas y repositorios de disertaciones y tesis. Se incluyeron publicaciones que respondieron a la pregunta de investigación, cumplieron con el objetivo del estudio y estaban disponibles en su totalidad en formato electrónico, en cualquier idioma. Resultados: la muestra estuvo compuesta por 28 estudios, 14 de los cuales fueron publicados en los Estados Unidos de América. Los trastornos mentales comunes encontrados fueron depresión, ansiedad, estrés postraumático y trastornos del estado de ánimo. Se mencionaron 20 síntomas, entre los más prevalentes se encuentran fatiga y trastornos del sueño/insomnio. Conclusiones: se destacó la dificultad e importancia de realizar el diagnóstico diferencial de estos trastornos, ya que sus síntomas pueden confundirse con otros problemas de salud y tienen un fuerte potencial de interferir en la evolución del paciente.

RESUMO Objetivo: mapear os transtornos mentais comuns recorrentes em pacientes submetidos ao transplante de células-tronco hematopoéticas. Métodos: trata-se de revisão de escopo realizada em janeiro de 2022 em bases de dados eletrônicas e repositórios de dissertações e tese. Foram incluídas publicações que respondessem à questão de pesquisa, atendessem ao objetivo do estudo e que estivessem disponíveis na íntegra em meio eletrônico, em qualquer idioma. Resultados: a amostra foi composta por 28 estudos, dos quais 14 foram publicados nos Estados Unidos da América. Os transtornos mentais comuns encontrados foram os transtornos depressivos, de ansiedade, estresse pós-traumático e de humor. Foram citados 20 sintomas, entre os mais prevalentes estão a fadiga e distúrbios do sono/insônia. Conclusões: evidenciaram-se a dificuldade e a importância de realizar o diagnóstico diferencial desses transtornos, uma vez que seus sintomas podem ser confundidos com outros problemas de saúde e têm forte potencial para interferir na evolução do paciente.

Insuficiencia cardiaca secundaria a amiloidosis AL: diagnóstico y tratamiento / Heart failure secondary to amyloidosis AL: diagnosis and treatment

Resumen La amiloidosis por depósito de cadenas livianas de inmunoglobulinas (AL) es una enfermedad poco frecuen te y subdiagnosticada. El mejor tratamiento disponible al momento es el trasplante autólogo de médula ósea (TMO). El compromiso cardíaco es el principal determi nante pronóstico en esta patología y en ocasiones un impedimento para recibir el TMO. Se presenta el caso de un varón de 44 años que consultó por signos y síntomas de insuficiencia cardiaca (IC) con biomarcadores cardia cos elevados. Se realizó un ecocardiograma transtorácico donde se objetivó aumento de espesores parietales con hipoquinesia global y fracción de eyección deteriorada en grado leve (50%). El paciente se internó en unidad coronaria para balance negativo y para estudio etiológico del cuadro. Ante la sospecha de enfermedad infiltrativa, se solicitaron un centellograma óseo con pirofosfato y cadenas livianas libres en suero. El centellograma óseo resultó no sugestivo para amiloidosis por transtiretina y las cadenas livianas libres mostraron una relación me nor a 0.26 con predominio lambda. Se realizó una biopsia de encía que confirmó el diagnóstico de amiloidosis AL. Posterior al diagnóstico comenzó tratamiento qui mioterápico específico con Ciclofosfamida, Bortezomib y Dexametasona (esquema CYBORD) y Daratumumab. Evolucionó con IC refractaria por lo que ingresó a lista de trasplante cardiaco, recibiendo el mismo al poco tiempo con buena evolución. Esto permitió reiniciar el esquema quimioterápico y en segundo término finalmente recibir el TMO, con buena evolución.

Abstract Light chain amyloidosis (AL) is a rare and underdi agnosed disease. The best treatment available is au tologous bone marrow transplantation (BMT). Cardiac involvement is the main prognostic determinant in this pathology and sometimes an impediment to re ceive BMT. We present a clinical case of a 44-year-old who consulted for signs and symptoms of heart failure (HF) with elevated cardiac biomarkers. A transthoracic echocardiogram showed increased wall thickness with global hypokinesia and mildly impaired ejection fraction (50%). The patient was admitted to the coronary unit for treatment with diuretics and for etiological study of the condition. In view of the suspicion of infiltrative disease, a bone scintigraphy with pyrophosphate and free light chains in serum were requested. The bone scintigraphy was not suggestive of transthyretin amyloidosis and the free light chains showed a ratio of less than 0.26 with lambda predominance. A gum biopsy was per formed and confirmed the diagnosis of AL amyloidosis. After diagnosis, specific chemotherapy treatment with Cyclophosphamide, Bortezomib and Dexamethasone (CYBORD scheme) and Daratumumab was started. He evolved with refractory HF so it was decided to admit him to the cardiac transplantation list, receiving the same soon after, with good evolution. This allowed the patient to restart the chemotherapy regimen and finally receive BMT, with good evolution.

Calidad de vida y toxicidad financiera de los receptores de trasplantes de células madre hematopoyéticas en COVID-19 / Quality of life and financial toxicity of hematopoietic stem cell transplant recipients in COVID-19 / Qualidade de vida e toxicidade financeira dos transplantados de células-tronco hematopoéticas na COVID-19

Objetivo: evaluar y correlacionar la calidad de vida y la toxicidad financiera de pacientes adultos sometidos a trasplante de células madre hematopoyéticas durante el período de la pandemia de COVID-19. Método: estudio observacional, analítico, realizado con 35 pacientes en un hospital de referencia para trasplante en Latinoamérica. Para la recolección de datos, se utilizaron los cuestionarios Functional Assessment Cancer Therapy Bone Marrow Transplantation y el COmprehensive Score for financial Toxicity. Para el análisis de los datos se utilizaron las pruebas de correlación de Spearman y Mann-Whitney. Resultados: la calidad de vida general durante la COVID-19 mostró un puntaje bajo (67,09/108) con mayor deterioro en el bienestar funcional (14,47/28), bienestar social (16,76/28) y preocupaciones adicionales (23,41/40). Los promedios del grupo alogénico fueron inferiores a los del grupo autólogo en todos los dominios, presentando diferencia significativa en relación a preocupaciones adicionales (p=0,01) y en el índice de evaluación del tratamiento (p=0,04). Se consideró que la toxicidad financiera tenía un impacto leve (22.11/44). Se observó una relación, aunque no significativa, entre la calidad de vida y la toxicidad financiera (p=0,051). Conclusión: la calidad de vida de la muestra fue baja; existe una correlación entre la calidad de vida y la toxicidad financiera, aunque no significativa. Cuanto mayor es la toxicidad financiera, menor es la calidad de vida.

Objective: to evaluate and correlate the quality of life and financial toxicity of adult patients undergoing hematopoietic stem cell transplantation during the COVID-19 pandemic. Method: observational, analytical study, carried out with 35 patients in a reference hospital for transplantation in Latin America. For data collection, the Functional Assessment Cancer Therapy Bone Marrow Transplantation and COmprehensive Score for Financial Toxicity questionnaires were used. Spearman and Mann-Whitney correlation tests were used for data analysis. Results: general quality of life during COVID-19 had a low score (67.09/108) with greater impairment in functional well-being (14.47/28), social well-being (16.76/28) and additional concerns (23.41/40). The means of the allogeneic group were lower than those of the autologous group in all domains, showing a significant difference in relation to additional concerns (p=0.01) and in the treatment evaluation index (p=0.04). Financial toxicity was considered to have a slight impact (22.11/44). There was a relationship, albeit not significant, between quality of life and financial toxicity (p=0.051). Conclusion: the quality of life of the sample was low; there is a correlation between quality of life and financial toxicity, although not significant. The higher the financial toxicity, the lower the quality of life.

Objetivo: avaliar e correlacionar a qualidade de vida e a toxicidade financeira dos pacientes adultos submetidos ao transplante de células-tronco hematopoéticas no período da pandemia de COVID-19. Método: estudo observacional, analítico, realizado com 35 pacientes em um hospital de referência para o transplante na América Latina. Para coleta de dados, utilizaram-se os questionários Functional Assessment Cancer Therapy Bone Marrow Transplantation e COmprehensive Score for financial Toxicity. Na análise dos dados empregaram-se os testes de correlação de Spearman e Mann-Whitney. Resultados: a qualidade de vida geral, durante a COVID-19, apresentou baixo escore (67,09/108), com maior comprometimento nas funções bem-estar funcional (14,47/28), social (16,76/28) e preocupações adicionais (23,41/40). As médias do grupo alogênico foram inferiores às do autólogo em todos os domínios, apresentando diferença significativa em relação às preocupações adicionais (p=0,01) e ao índice de avaliação do tratamento (p=0,04). A toxicidade financeira foi considerada de impacto leve (22,11/44). Observou-se relação, ainda que não significativa, entre a qualidade de vida e a toxicidade financeira (p=0,051). Conclusão: a qualidade de vida da amostra foi baixa, logo há uma correlação entre qualidade de vida e a toxicidade financeira, embora não significativa. Quanto maior a toxicidade financeira, menor a qualidade de vida.

Doença granulomatosa crônica: características clínicas, seguimento e terapêutica de cinco pacientes pediátricos / Chronic granulomatous disease: clinical characteristics, follow-up, and therapy of 5 pediatric patients

Introdução: A doença granulomatosa crônica (DGC) é caracterizada por um defeito na capacidade microbicida das células fagocíticas (monócitos e neutrófilos), com alta mortalidade se não diagnosticada precocemente. Os pacientes apresentam infecções recorrentes ou graves, suscetibilidade a granulomas em órgãos profundos, doenças autoimunes e doença inflamatória intestinal. Objetivo e Método: Relato de aspectos clínicos e do tratamento de cinco pacientes com doença granulomatosa crônica. Resultados: Cinco pacientes, três meninos, medianas de idade no início dos sintomas e diagnóstico de 8 meses e 48 meses, respectivamente, foram estudados por um período de 10 anos. Pneumonia (5/5) e doença micobacteriana (3/5) foram as manifestações iniciais mais comuns. Alterações pulmonares foram observadas em todos os casos. Mutações nos genes CYBB e NCF1 foram identificadas em três casos. Antibioticoprofilaxia foi instituída em todos os pacientes e três foram submetidos ao transplante de células tronco-hematopoiéticas (TCH), aos 7, 18 e 19 anos e com sobrevida atual entre 4 a 5 anos. Conclusão: O monitoramento cuidadoso de infecções graves com tratamento imediato foi crucial para a sobrevivência. O TCH, mesmo ao final da adolescência, promoveu a cura da DGC em três pacientes.

Introduction: Chronic granulomatous disease (CGD) is characterized by a defective microbicidal capacity of phagocytic cells (monocytes and neutrophils) with high mortality if not early diagnosed. Patients have recurrent or severe infections and are susceptible to granulomas in visceral organs, autoimmune diseases, and inflammatory bowel diseases. Objective and Method: To report the clinical features and treatment of 5 patients with CGD. Results: Five patients, 3 boys, with median ages at symptom onset and diagnosis of 8 months and 48 months, respectively, were followed for 10 years. Pneumonia (5/5) and mycobacterial disease (3/5) were the most common initial manifestations. Pulmonary changes were observed in all cases. Mutations in the CYBB and NCF1 genes were identified in 3 cases. All patients received antibiotic prophylaxis. Three patients underwent a hematopoietic stem cell transplant (HSCT) at 7, 18, and 19 years, with current survival of 4 to 5 years. Conclusion: Careful monitoring for severe infection with prompt treatment was crucial for survival. Even though HSCT was performed in late adolescence, it promoted the cure of CGD in 3 patients.

Detection of focal lesions in the clot section with negative bone marrow aspirate and trephine biopsy—A series of 5 cases

Bone marrow aspiration and trephine biopsies are commonly used procedures in clinical practice. The practice of making a clot section by using the leftover blood from the bone marrow aspirate material is not a commonly followed practice across centers. A clot section has the advantage of studying the added material with an increased possibility of detecting focal lesions such as myeloma, lymphoma, granuloma, and metastasis in the bone marrow. Bone marrow aspirate, trephine biopsy, and clot section were compared for the detection of focal lesions in a series of 5 patients, 3 of who presented with a history of fever and 2 were already diagnosed cases of Hodgkin lymphoma. Focal lesions were detected in the 5 cases in the clot section alone, whereas bone marrow aspirate and trephine biopsy did not show any focal lesion. Granulomatous infiltration was detected in 3 patients, and lymphomatous infiltration was detected in 2 patients in the clot section, whereas bone marrow aspirate and trephine biopsy were negative for any focal lesion in all 5 cases. A clot section is particularly useful in the detection of bone marrow lesions with a focal distribution. Hence, it must be studied alongside bone marrow aspirate smears, touch smears, and trephine biopsy to increase the diagnostic yield.

Survival benefit of pediatric-based regimen for adults with acute lymphoblastic leukemia: A single-center retrospective cohort

ABSTRACT Introduction: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. Methods: Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. Results: The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p = 0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p = 0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p = 0.0007 and p = 0.004, respectively). Conclusion: ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.

Metastasis of primary signet ring cell carcinoma of prostate to bone marrow: A rare occurrence with review of literature

We report a case of a 65-year-old male who presented with multiple enlarged intraabdominal lymph nodes with lytic lesions over pelvic and lumbar vertebrae. His serum prostate-specific antigen (PSA) was markedly raised. Bone marrow investigation revealed the presence of diffuse infiltration of single cells having hyperchromatic nuclei, moderate amount of eosinophilic cytoplasm, and eccentrically placed nuclei resembling signet ring cells. Hence, a diagnosis of metastatic signet cell carcinoma of prostate was made on bone marrow biopsy. This variant of prostatic carcinoma is very rare and accounts for only 2.5% of all prostatic adenoacarcinomas that make our case worth reporting. To emphasize the rare occurrence of this variant, we performed a Pubmed-based literature review of 25 years.

New cost-effective human leukocyte antigen testing algorithm for screening of human leukocyte antigen-matched related donor in thalassemia major patient pretransplant workup: A single-center study from resource-constrained settings

Introduction: India has a huge disease burden of thalassemia major with an estimated 40 million carriers and over a million thalassemia major patients. Very few patients are optimally treated, and the standard of care “hematopoietic stem cell transplant” (HSCT) is out of reach for most patients and their families. The cost of HSCT is significant, and a substantial proportion of it goes to human leukocyte antigen (HLA) testing of family members (HLA screening) in hope of getting a matched related donor (MRD) for HSCT. The aim of this study was to establish that a new proposed testing algorithm of HLA typing would be more cost-effective as compared to the conventional HLA screening within MRD families for possible HSCT. Material and Methods: Buccal swab samples of 177 thalassemia patients and their prospective family donors (232) were collected. Using a new HLA testing algorithm, samples were tested for HLA typing in a sequential manner (first HLA-B, then HLA-A, and finally HLA-DR) using the sequence-specific oligonucleotide probe method on the Luminex platform. Results: The new sequential HLA-A, HLA-B, and HLA-DRB1 testing algorithm showed a 49.1% reduction in cost compared to the conventional HLA testing algorithm. Furthermore, 40 patients (22.59%) were found to have HLA-MRD within the family among other samples that were tested. Conclusion: The new HLA testing algorithm proposed in the present study for identifying MRD for HSCT resulted in a substantial reduction in the cost of HSCT workup.

One-year mortality of hematopoietic stem cell recipients admitted to an intensive care unit in a dedicated Brazilian cancer center: a retrospective cohort study

ABSTRACT BACKGROUND: Hematopoietic stem cell transplantation (HSCT) recipients requiring intensive care unit (ICU) admission early after transplantation have a poor prognosis. However, many studies have only focused on allogeneic HSCT recipients. OBJECTIVES: To describe the characteristics of HSCT recipients admitted to the ICU shortly after transplantation and assess differences in 1-year mortality between autologous and allogeneic HSCT recipients. DESIGN AND SETTING: A single-center retrospective cohort study in a cancer center in Brazil. METHODS: We included all consecutive patients who underwent HSCT less than a year before ICU admission between 2009 and 2018. We collected clinical and demographic data and assessed the 1-year mortality of all patients. The effect of allogeneic HSCT compared with autologous HSCT on 1-year mortality risk was evaluated in an unadjusted model and an adjusted Cox proportional hazard model for age and Sequential Organ Failure Assessment (SOFA) at admission. RESULTS: Of the 942 patients who underwent HSCT during the study period, 83 (8.8%) were included in the study (autologous HSCT = 57 [68.7%], allogeneic HSCT = 26 [31.3%]). At 1 year after ICU admission, 21 (36.8%) and 18 (69.2%) patients who underwent autologous and allogeneic HSCT, respectively, had died. Allogeneic HSCT was associated with increased 1-year mortality (unadjusted hazard ratio, HR = 2.79 [confidence interval, CI, 95%, 1.48-5.26]; adjusted HR = 2.62 [CI 95%, 1.29-5.31]). CONCLUSION: Allogeneic HSCT recipients admitted to the ICU had higher short- and long-term mortality rates than autologous HSCT recipients, even after adjusting for age and severity at ICU admission.

Utility of morphologic assessment of bone marrow biopsy in diagnosis of lysosomal storage disorders

Introduction: Lysosomal storage disorders (LSDs) are rare disorders and pose a diagnostic challenge for clinicians owing to their generalized symptomatology. In this study, we aim to classify LSDs into two broad categories, namely, Gaucher disease (GD) and Niemann–Pick/Niemann–Pick-like diseases (NP/NP-like diseases) based on the morphology of the storage cells in the bone marrow (BM) aspiration smears and trephine biopsy sections. Materials and Method: This retrospective study includes 32 BM specimens morphologically diagnosed as LSDs at our institute, in the last 10 years. Subsequently, they were subclassified into GD and NP/NP-like diseases. Further, we have compared and analyzed the clinical, hematological, and biochemical parameters for the two groups of LSDs. Results: Based on BM morphology, 59.4% (n = 19) cases were diagnosed as NP/NP-like diseases and 40.6% (n = 13) cases as GD. Abdominal distension and failure to thrive were the most common clinical manifestations in both groups of LSDs. Anemia and thrombocytopenia were frequently seen in either of the LSDs. On the assessment of metabolic profile, elevated total/direct bilirubin and liver enzymes were more commonly seen in NP/NP-like diseases when compared with GD. Conclusion: We have classified LSDs into GD and NP/NP-like diseases based on the morphology of the storage cells in the BM specimen. The hallmark findings on BM biopsy annexed with the comparative features of the two proposed categories can aid the clinician in clinching the diagnosis. Formulation of such a methodology will prove instrumental for patient care in an underresourced setting.

History and legal aspects of bone marrow donor banks in Brazil

INTRODUCTION: Bone marrow transplants primarily depend on people who previously registered to be donors. From then on, the search for compatibility between donor and recipient begins. OBJECTIVE: To describe the historical landmarks and the legal apparatus of bone marrow donor banks in Brazil based on an integrative review. METHODS: LILACS database and PubMed and SciELO journals were used. The term bone marrow transplantation was the descriptor. Eligibility criteria were: articles with the theme of Bone Marrow Transplantation (BMT) and studies carried out on the national territory. RESULTS: A total of 88,855 articles were identified, among which 185 met the eligibility criteria. After they were thoroughly read, 14 articles were selected. The studies pointed out fragments that dealt with important historical landmarks for the establishment of bone marrow transplantation as a conventional treatment for oncohematological diseases. CONCLUSION: The use of BMT has a history of more than thirty years in Brazil. However, none of the articles identified specifically addresses the historical content of bone marrow transplantation.

EVALUATION OF PANCYTOPENIA WITH BONE MARROW INTERPRETATION

Background: Pancytopenia is one of the most common clinico-haematological entity observed in our day to day clinical practice. It is a disorder in which all the three major elements of blood (i.e. red blood cells, white blood cells and platelets) are decreased in number. The causes of pancytopenia may be due to decrease in hematopoietic cell production in the marrow resulting from infections, toxins, malignant cell in?ltration, post- chemotherapy or post-radiation. Aims and Objectives: 1) To study the etiology and clinical presentation of pancytopenia in all age groups. 2) To correlate with bone marrow interpretation Materials & Methods: This is a prospective study which was conducted among 50 patients of pancytopenia in the Clinical Pathology, Government General Hospital,Kurnool from January 2021 to October 2022 Bone marrow aspiration was done by using Salah's bone marrow puncture needle. Smears were made from bone marrow aspirate (BMA) and stained by Leishman stain and special stains like Perl`s wherever necessary. The smears were assessed for cellularity, differentiation and maturation of erythroid, myeloid and megakaryocytic lineage, M:E ratio, Plasma cells, Lymphocytes and parasites/ abnormal cells. In the present study the commonest cause of Pancytopenia was Megaloblastic anemia (70%) followed by Results: Dimorphic anemia (20%). The less common conditions were Multiple Myeloma (6%),Chronic Myeloid Leukemia(2%),Acute Leukemia(2%). The present study concludes that complete primary hematological Interpretation and Conclusion: investigations along with bone marrow aspiration in pancytopenic patients are helpful for understanding disease process and to diagnose or to the rule out causes of pancytopenia. These are also helpful in planning for further investigations and management

Spectrum-of-haematological-disorders-in-bone-marrow-aspiration-at-tertiary-care-hospital-jorhat

Anemia is a common symptom of haematological disorders in people of all ages .The spectrum of haematological disorders differs significantly between developing and industrialized countries. The primary use of bone marrow aspirate is for cytological examination. It enables study into the cellularity of the bone marrow as a whole, the detection of specific lesions, and the amount of infiltration by various disease entities. The aim of the study is toAims & objective: evaluate the spectrum of haematological disorders reported in bone marrow aspiration and to know the age and sex incidence. This prospective study is an observational study was conducted over a one-yearMaterials and methods: period on 73 patients and the spectrum of hematological disorders was studied on bone marrow aspiration smears. Conclusion: A thorough examination of the bone marrow is essential for diagnosing haematologic disorders. It is a simple and cost effective procedure which can be performed routinely without using any specialized equipment or a need of general anaesthesia

Leishmaniasis visceral. Presentación de un caso y revisión de la entidade

La leishmania la describieron Leishman y Donovan en 1903, al aislar el parásito del bazo de las personas afectadas. La leishmaniasis es una enfermedad tropical y subtropical, causada por un protozoo intracelular del género Leishmania y transmitida a los humanos por la picadura de vectores Lutzomyias infectadas. Tiene como reservorios a los perros, roedores, lobos, zorros y el humano como huésped incidental. Clínicamente la leishmaniasis puede clasificarse en tres formas principales: leishmaniasis cutánea (LC), localizada (LCL) o difusa (LCD), leishmaniasis destructiva mucocutánea (LMC) y leishmaniasis visceral (LV o Kala-Azar). La enfermedad se manifiesta clínicamente con la invasión del parásito y daño en funcionamiento de órganos vitales como son la médula ósea, el hígado y el bazo. Se presenta el caso de un paciente masculino adolescente de 11 anos de edad de zona rural que presenta un cuadro clínico de aumento de volumen de abdomen superior, palidez marcada, decaimento, con hepato y esplenomegalia atendido en Bahía, Brasil en 2018 con diagnóstico de leishmaniasis. Se describe la clínica, médios diagnósticos y tratamiento.

Leishmania was described by Leishman and Donovan in 1903, when the parasite was isolated from the spleen of affected people. Leishmaniasis is a tropical and subtropical disease, caused by an intracellular protozoan of the genus Leishmania and transmitted to humans by the bite of infected Lutzomyia vectors. It has as reservoirs dogs, rodents, wolves, foxes and humans as incidental hosts. Clinically, leishmaniasis can be classified into three main forms: cutaneous (LC), localized (LCL) or diffuse (LCD) leishmaniasis, mucocutaneous destructive leishmaniasis (CML), and visceral leishmaniasis (VL or Kala-Azar). The disease manifests clinically with the invasion of the parasite and damage to the functioning of vital organs such as the bone marrow, liver and spleen.We present the case of an 11-year-old adolescent male patient from rural areas who presented a clinical picture of increased volume of the upper abdomen, marked pallor, decay, with hepato and splenomegaly treated in Bahia, Brazil in 2018 with a diagnosis of leishmaniasis. The clinic, diagnostic methods and treatment are described.

A leishmania foi descrita por Leishman e Donovan em 1903, quando o parasita foi isolado do baço das pessoas afetadas. A leishmaniose é uma doença tropical e subtropical, causada por um protozoário intracelular do gênero Leishmania e transmitida aos seres humanos pela picada de vetores de Lutzomyia infectados. Tem como reservatórios cães, roedores, lobos, raposas e humanos como hospedeiros incidentais. Clinicamente, a leishmaniose pode ser classificada em três formas principais: leishmaniose cutânea (LCL), localizada (LCL) ou difusa (LCD), leishmaniose mucocutânea destrutiva (LMC) e leishmaniose visceral (LV ou Kala-Azar). A doença se manifesta clinicamente com a invasão do parasita e danos ao funcionamento de órgãos vitais, como a medula óssea, fígado e baço.Apresentamos o caso de um adolescente de 11 anos, do sexo masculino, de áreas rurais, que apresentou quadro clínico de aumento do volume do abdome superior, palidez acentuada, cárie, com hepato e esplenomegalia tratado na Bahia, Brasil, em 2018, com diagnóstico de leishmaniose. A clínica, os métodos de diagnóstico e o tratamento são descritos.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

Research progress on the bone-marrow sparing intensity-modulated radiotherapy for cervical cancer / 中华放射肿瘤学杂志

The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.

Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging / 中华放射肿瘤学杂志

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Comparative study of the radiosensitivity of hematopoietic stem/progenitor cells derived from fetal liver and bone marrow / 中华放射医学与防护杂志

Objective:To investigate the difference in the radiation sensitivity of hematopoietic stem and progenitor cells (HSPCs) derived from fetal liver and bone marrow.Methods:HSPCs from fetal liver of 14.5 d embryo or bone marrow of 8 week-old mice were isolated to receive a single dose of 5 or 10 Gy irradiation in vitro using a 60Co irradiator. Twelve hours later, the cell apoptosis, mitochondrial reactive oxygen species (ROS) level, colony formation ability and DNA damage in HSPCs were detected. Freshly isolated HSPCs were injected into lethally irradiated CD45.1 + C57BL/6J mice (4.5 Gy+ 5 Gy with an interval of 30 min) Chimerism rate, lineage constitution, and cell cycle were analyzed 12 weeks after transplantation. Results:Compared with bone marrow HSPCs after irradiation, the percentage of apoptosis in fetal liver HSPCs was significantly higher ( t=16.21, 12.27, P<0.05), the level of ROS was dramatically elevated ( t=68.72, 18.89, P<0.05). At 10 Gy, fetal liver HSPCs could not form colonies at all ( t=12.41, 15.67, 9.46, P<0.05). γ-H2AX immunofluorescence staining showed that the DNA damage of fetal liver HSPCs was more severe after irradiation, and the number of Foci formed was significantly higher than that of bone marrow HSPCs ( t=2.27, 2.03, P< 0.05), which indicated that fetal liver HSPCs were more sensitive to radiation. The chimerism rate of transplanted fetal liver HSPCs was lower than that of bone marrow cells ( t=5.84, P<0.05) with a higher proportion of myeloid lineage, suggesting that fetal liver HSPCs had lower in vivo reconstitution capacity than bone marrow HSPCs and were more prone to myeloid differentiation. The cell cycle of bone marrow HSPCs from transplanted chimeric mice was examined, and the proportion of S-phase was significantly higher in the fetal liver group than that in the bone marrow group ( t=2.89, P<0.05). Mitochondrial stress results showed that fetal liver HSPCs had higher basal respiratory capacity ( t=39.19, P<0.05), proton leakage ( t=6.64, P<0.05), ATP production ( t=9.33, P<0.05), and coupling efficiency ( t=7.10, P<0.05) than bone marrow c-Kit + cells, while respiratory reserve capacity ( t=5.53, P< 0.05) was lower than that of bone marrow c-Kit + cells. Conclusions:HSPCs derived from fetal liver display higher radiosensitivty compared with bone marrow HSPCs, laying the foundation for an in-depth illustration of the effects of radiation on hematopoietic stem cells at different developmental stages.

Relationship between the pelvic bone marrow dose-volume parameters and acute hematologic toxicity in neoadjuvant pelvic intensity-modulated radiotherapy for local advance rectal cancer / 中华放射医学与防护杂志

Objective:To analyze the correlation between the volume of irradiated pelvic bone marrow and acute hematologic toxicity (HT), in order to provide clinical data to reduce the risk of acute HT and optimize the radiotherapy plan.Methods:From October 2017 to May 2019, 41 LARC patients who received neoadjuvant concurrent chemoradiotherapy (CCRT) were retrospectively reviewed in our center. All patients were treated with 5-field intensity-modulated radiotherapy (IMRT), and the prescription dose delivered to PTV was 45-50.4 Gy in 25-28 fractions. Capecitabine or 5-fluorouracil (5-FU) wasadministered daily 5 days a week during radiotherapy. Different HTswere recorded according to National Cancer Institute Common Toxicity Criteria Version 5.0 (NCI-CTC.V5.0) based on laboratory tests. The volume of PBM or each site (coxal, sacrum, femoral) receiving more than x Gy refers to as TVx, CVx, SVx, and FVx, respectively. Logistic regression was performed to evaluate the association between the volume of irradiated pelvic bone marrow and different HT. Generalized additive model (GAM) and piecewise regression were used to further analyze the possible nonlinear relationship and threshold effect between them. Results:Multivariate logistic regression analysis showed that low-dose of irradiated total pelvic bone marrow volume ( TV5) and coxal bone marrow volume ( CV5, CV10) were significantly correlated with Grade ≥2 leukopenia( P<0.05). There was a significant negative correlation between the sacrum bone marrow volume ( SV5, SV10) and Grade ≥2 leukopenia ( P<0.05). A thresholdeffect has been observed between CV10 and Grade ≥2 leukopenia by Generalized additive model (GAM) and piecewise linear regression. The threshold between CV10 and Grade ≥2 leukopenia was 575 ml, OR (95% CI) was 1.85 (1.08, 3.16). Conclusions:In neoadjuvant IMRT of rectal cancer, CV is a better predictor of acute HT induced by CCRT than TV. The irradiated volume of CV associated with acute HT was mainly low-dose levels ( CV5, CV10). The thresholds of our study ( CV10= 575 ml) could be a good reference for the optimization of the radiotherapy plan.