Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens.@*RESULTS@#The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05).@*CONCLUSION@#PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.

Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma.@*METHODS@#The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection.@*RESULTS@#A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection.@*CONCLUSIONS@#Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.

Heterocyclic compounds and phenolic glycosides from flowers of Dendrobium officinale / 中国中药杂志

Eight heterocyclic compounds and twelve phenolic glycosides were separated from the water extract of Dendrobium officinale flowers through chromatographic techniques, such as Diaion HP-20 macroporous adsorption resin column chromatography(CC), silica gel CC, ODS CC, Sephadex LH-20 CC, and preparative high performance liquid chromatography(PHPLC). According to the spectroscopic analyses(MS, ~1H-NMR, and ~(13)C-NMR) and optical rotation data, the compounds were identified as dendrofurfural A(1), 2'-deoxyadenosine(2), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid(3), 4-[2-formyl-5-(methoxymethyl)-1H-pyrrol-1-yl] butanoic acid(4), 1-(2-hydroxyethyl)-5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde(5), 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde(6), methyl 5-(hydroxymethyl)-furan-2-carboxylate(7),(S)-5-hydroxymethyl-5H-furan-2-one(8), 2-methoxyphenyl-1-O-β-D-glucopyranoside(9), arbutin(10), isotachioside(11), 2,6-dimethoxy-4-hydroxyphenol-1-O-β-D-glucopyranoside(12), orcinol glucoside(13), tachioside(14), gastrodin(15), 4-O-β-D-glucopyranosylvanillyl alcohol(16), 2,6-dimethoxy-4-hydroxymethylphenol-1-O-β-D-glucopyranoside(17), icariside D_2(18), 4-formylphenyl-β-D-glucopyranoside(19), and vanillin-4-O-β-D-glucopyranoside(20). Among them, compound 1 is a new furfural benzyl alcohol condensate, with the skeleton first found in Dendrobium. Compounds 2-9, 11, 13, and 19 are reported from Dendrobium for the first time, and compounds 14 and 18 are reported for the first time from D. officinale. Compounds 11 and 14 showed moderate DPPH radical scavenging capacity, and compounds 11-14 demonstrated potent ABTS radical scavenging capacity, possessing antioxidant activity.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Colchicina, perspectivas de un viejo amigo para la reumatología en la COVID-19: una revisión exploratoria / no

Introducción: La colchicina es ampliamente utilizada en enfermedades inflamatorias como la gota y la fiebre mediterránea familiar. Debido a su capacidad inmunomoduladora, podría tener un papel importante en el tratamiento de la COVID-19. Objetivo: Explorar la evidencia médica publicada hasta el 28 de diciembre del 2020, acerca de la eficacia y la seguridad de la colchicina en el tratamiento de pacientes con infección confirmada por SARS-CoV-2. Material y métodos: Revisión exploratoria de la literatura que incluyó PubMed y Scopus. Se tuvieron en cuenta registros de ensayos clínicos y publicaciones con datos empíricos (estudios observacionales y experimentales) en inglés y español. Resultados: Se encontraron 33 ensayos clínicos y 6 publicaciones empíricas: estudios de cohorte prospectivos (n = 2) y retrospectiva (n = 2), ensayo clínico aleatorizado (n = 1) y estudio casos y controles (n = 1). La suma de los participantes en los ensayos es de 46.324 individuos, el 73% (24/33) de los estudios recluta a la población de estudio y el 51% (17/33) son fase 3. Conclusiones: Un ensayo clínico respalda la disminución en marcadores inflamatorios pronósticos y el tiempo de estancia hospitalaria en la infección por SARS-CoV-2. Los ensayos clínicos en desarrollo ayudarán a esclarecer la eficacia y la seguridad de la colchicina para el manejo de pacientes con COVID-19.

Introduction: Colchicine is widely used to treat inflammatory diseases such as gout and Mediterranean fever. Due to its immunomodulatory capacity, it could play an important role in the treatment of COVID-19. Objective: To explore the current available medical evidence, published until 28 December 2020, regarding the efficacy and safety of colchicine in the treatment of patients with confirmed SARS-CoV-2 infection. Material and methods: Scoping review of the literature that included PubMed and Scopus. Records of clinical trials and publications with empirical data (observational and experimental studies) in English and Spanish were included. Results: A total of 33 clinical trials and 6 publications were found: prospective (n = 2) and retrospective (n = 2) cohort studies, randomised clinical trials (n = 1) and case-control studies (n = 1). The total number of participants in the trials is 46,324 individuals, 73% (24/33) of the studies are recruiting participants and 51% (17/33) are phase 3 studies. Conclusions: One clinical trial reports a decrease in prognostic inflammatory markers and length of hospital stay in SARS-CoV-2 infection. The ongoing clinical trials will clarify the efficacy and safety of colchicine for the management of patients with COVID-19.

Systemic lupus erythematosus: Pharmacological differences between women and men and among age groups and geographical regions

Systemic lupus erythematosus (SLE) is a chronic and potentially fatal autoimmune disease. There are clinical differences between women and men and among age groups. Its treatment involves a heterogeneous group of drugs. The objective was to determine the pharmacological treatment patterns in a group of patients with SLE and compare them according to sex, age group and geographic region. This was a cross-sectional study that identified outpatient drugs used in patients with SLE from a population database of Colombians affiliated with the Colombian Health System. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. A total of 4307 patients with SLE were identified (median age, 44.2 years; 89.4% women). Disease-modifying antirheumatics were the most prescribed drugs (90.5%), especially chloroquine (54.4%), which predominated in all age groups and geographical regions. Hydroxychloroquine and methotrexate were the predominant prescribed drugs for women, while corticosteroids, chloroquine, azathioprine, and mycophenolate were the predominant prescribed drugs for men. The use of corticosteroids (prednisolone and prednisone) decreased with increasing age. Differences were found in the prescription of drugs for patients with SLE between women and men and among geographic regions and age groups. The use of chloroquine predominated over hydroxychloroquine, contrasting with clinical practice guidelines.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune crónica y potencialmente mortal. Existen diferencias clínicas entre mujeres y hombres, y entre grupos de edad. Su tratamiento involucra un grupo heterogeneo de medicamentos. El objetivo fue determinar los patrones de tratamiento farmacológico de un grupo de pacientes con LES y compararlos según el sexo, los grupos de edad y las regiones geograficas. Estudio de corte transversal que identifico los medicamentos de uso ambulatorio empleados en pacientes con LES, a partir de una base de datos poblacional de colombianos afiliados al Sistema de Salud de Colombia. Se consideraron variables sociodemográficas y farmacologicas. Se realizo un análisis descriptivo y bivariado. Se identificó a 4.307 pacientes con LES, con una mediana de edad 44,2 an˜ os y un 89,4% mujeres. Los medicamentos modificadores de enfermedad reumatica fueron los mas prescritos (90,5%), en especial cloroquina (54,4%), el cual predomino en todos los grupos de edad y las regiones geográficas. La hidroxicloroquina y el metotrexato predominaron en mujeres, mientras que los corticosteroides, la cloroquina, la azatioprina y el micofenolato, en hombres. Con el aumento de la edad disminuyo el uso de corticoides (prednisolona y prednisona). Se encontraron diferencias en la prescripción de los medicamentos empleados en los pacientes con LES entre mujeres y hombres, regiones geográficas y grupos etarios. El uso de cloroquina predomino sobre la hidroxicloroquina, en contraste con lo recomendado por las guías de practica clínica.

Verificación y transferencia de intervalos de referencia de variables bioquímicas de rutina / Verification and transfer of reference intervals of routine biochemical variables

Introducción. El correcto análisis en la interpretación de los resultados de cualquier analito biológico es esencial para la salud del paciente y está fuertemente ligado a contrastar dichos resultados con los intervalos biológicos referenciales que estén acorde a la población que está siendo analizada diariamente. El objetivo de este artículo, fue establecer intervalos referenciales (IR) en adultos para glicemia, urea, creatinina, ácido úrico, colesterol total y triglicéridos en un laboratorio clínico y comparar los valores obtenidos con los incluidos en los insertos para ese rango de edad. Metodología. La población fue de 561 adultos de ambos sexos, aparentemente sanos, que acudieron a Biomasterclin Laboratorio en Valencia, Venezuela, y cuyas edades fueron de 57,1±18,1 años. Resultados. Los IR obtenidos fueron glicemia 63,0-108,8 mg/dL, urea 17,7-54,9 mg/dL, creatinina 0,60-1,41 mg/dL, ácido úrico 0,89-7,26 mg/dL, colesterol total 78,5-251,1 mg/dL y triglicéridos 39,5-176,0 mg/dL. Los IR propuestos por la casa comercial empleada para la determinación de la glicemia y la creatinina pudieron ser transferidos a la población evaluada, mientras que el resto de los IR no. Conclusión. Debido a las diferencias que se presentan entre los IR en los estuches comerciales comparados con los de la población de individuos que acuden a los laboratorios clínicos, se hace necesario establecer IR para ser empleados en cada laboratorio clínico

The correct analysis in the interpretation of the results of any biological analyte is essential for the health of the patient and it is strongly linked to comparing those results with reference ranges that are in accordance with the population that is being analyzed on a daily basis. The objective of this study was to establish reference ranges in adults for glycemia, urea, creatinine, uric acid, total cholesterol and triglycerides in a clinical laboratory and compare the values obtained with those included in the inserts for the corresponding age group. Methodology. The population consisted of 561 apparently healthy adults of both sexes that attended Biomasterclin Laboratorio in Valencia, Venezuela, whose ages were 57.1±18.1 years. Results. The reference ranges obtained for glycemia were 63.0- 108.8 mg/dL, urea 17.7-54.9 mg/dL, creatinine 0.60-1.41 mg/dL, uric acid 0.89- 726 mg/dL, total cholesterol 78.5-251.1 mg/dL and triglycerides 39.5-176.0 mg/ dL. The reference ranges proposed by the commercial kits used for the determination of glycemia and creatinine could be transferred to the evaluated population, while the rest of the reference ranges could not. Conclusion. Due to the differences that occur between the reference ranges in commercial kits compared to those of the population of individuals who attend clinical laboratories, it is necessary to establish reference values in each clinical laboratory

A Single-Center Analysis of the Use of G-CSF Combined with Plerixafor to Mobilize Peripheral Blood Hematopoietic Stem Cell from Healthy Related Donors in Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To study the effect and safety of G-CSF combined with Plerixafor on the mobilization of peripheral blood hematopoietic stem cells from healthy related donors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#It was analyzed retrospectively that the data of peripheral blood hematopoietic stem cells from 33 (observation group) related donors mobilized by G-CSF plus Plerixafor in Hebei Yanda Lu Daopei Hospital from April 2019 to April 2021. Bone marrow and peripheral blood hematopoietic stem cells (PBSCs) of these donors were respectively collected on the fourth and fifth day of G-CSF-induced mobilization. Following the administration of Plerixafor on the night of the fifth day, PBSCs were collected on the sixth day once again. 46 donors using "G-CSF only" mobilization method in the same period were randomly selected as the control and respectively analyzed the differences of CD34+ cell counts on the fifth and the sixth day in two groups. And the donors' adverse reaction to Plerixafor in the form of questionnaire was also observed. Then it was compared that the patients who underwent allo-HSCT in "G-CSF+Plerixafor" group and "G-CSF only" group in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation.@*RESULTS@#CD34+ cells count (M±Q) among PBSCs collected on the fifth and the sixth day in the observation group were (1.71±1.02)×106/kg and (4.23±2.33)×106/kg, respectively. CD34+ cell counts on the sixth day was significantly higher than that of the fifth day (P<0.001); While the counterparts in the control group were (2.47±1.60)×106/kg and (1.87±1.37)×106/kg, respectively. By statistical analysis, CD34+ cell counts on the sixth day was significantly less than that of the fifth day (P<0.001). The adverse reaction to Plerixafor for the donors in the study were all grade 1 or 2 (mild or moderate) according to CTCAE 5.0 and disappeared in a short time. The patients who underwent allo-HSCT in the "G-CSF+Plerixafor" group and "G-CSF only" group were not statistically significant in terms of acute GVHD at grade I-IV or III-IV, CMV reactivation and EBV reactivation (P>0.1).@*CONCLUSION@#The cell mobilization program of G-CSF combined with Plerixafor is safe and effective for being applied to allo-HSCT. The addition of Plerixafor can significantly increase the number of CD34 postive cells in the PBSC collection. Key words　　; ;

Rabdomiólisis inducida por consumo crónico de bebidas energizantes asociado a ejercicio físico de baja intensidad: reporte de caso / Rhabdomyolysis induced by long-term consumption of energy drinks associated with low intensity physical exercise: case report

RESUMEN Introducción: Un riesgo potencialmente mortal es el hábito de consumo de bebidas energizantes, porque puede producir un síndrome caracterizado por la necrosis muscular que promueve la liberación de enzimas y mioglobina proveniente del interior del miocito hacia la circulación, creando una peroxidación lipídica llegando a generar lesión renal aguda e hyperkalemia; conocido como rabdomiólisis. La rabdomiólisis la esperaríamos encontrar entre 24 y 48 h después de actividades extenuantes, aún más con un índice de Borg modificado mayor o igual a 5 puntos; sin embargo, las bebidas energizantes por su alto contenido de cafeína y otros componentes pueden generar este evento adverso poco conocido. Caso clínico: Paciente de 37 arios, obeso, que ingresó al servicio de urgencias por cuadro clínico de mialgia y orina oscura que apareció 24h después de 4 días de ejercicio muscular de baja intensidad, asociado a consumo diario de bebida energizante por 2 años. El diagnóstico de rabdomiólisis se confirmó por hiperCKemia e hipertrasaminemia; no fue posible medir los niveles de mioglobina. El paciente fue tratado con fluidoterapia agresiva. Nunca presentó complicaciones renales ni hidroelectrolíticas. Conclusión: Nuestro caso destaca la aparición de rabdomiólisis aguda en pacientes sometidos a ejercicios de baja intensidad no descartando como causa principal el consumo crónico de bebidas energizantes. Son pocos casos actualmente reportados en la literatura. Gracias al tratamiento oportuno se evitó la progresión a lesión renal aguda.

ABSTRACT Introduction: The habit of consuming energy drinks is a life-threatening risk, because it can produce a syndrome characterised by a muscle necrosis. This promotes the release of enzy mes and myoglobin from inside the myocyte into the circulation, creating lipid peroxidation and leading to acute kidney injury, and hyperCKemia, together producing rhabdomyolysis. Rhabdomyolysis can be expected to be found within 24 to 48 h after strenuous activities, even more so with a modified Borg index greater than or equal to 5 points. However, energy drinks, due to their high content of caffeine and other components, can generate this little known adverse event. Clinical case: A 37-year-old patient admitted to the emergency department due to clinical symptoms of myalgia, and dark urine that appeared 24 h after four days of low-intensity muscular exercises, and was associated with daily consumption of an energizing drink for 2 years. The diagnosis of rhabdomyolysis was confirmed by increased creatine kinase and transaminases. It was not possible to measure myoglobin levels. The patient was treated with aggressive fluid therapy. He never presented with any renal or electrolyte complica tions. Conclusion: This case highlights the appearance of acute rhabdomyolysis in patients taking low intensity exercises, and not ruling out long-term consumption of energy drinks as the main cause. There are few cases currently reported in the literature. Owing to the timely treatment, progression to acute kidney injury was avoided.

Effect of triptolide in improving platelet activation in patients with ankylosing spondylitis by regulating VEGFA,SDF-1,CXCR4 pathway / 中国中药杂志

The effect of triptolide( TP) on VEGFA,SDF-1,CXCR4 pathway were investigated in vitro to explore the mechanism in improving platelet activation in patients with ankylosing spondylitis( AS). Peripheral blood mononuclear cells( PBMC) were used for the experiment and divided into 4 groups: normal group( NC),model group( MC),triptolide group( TP),and AMD3100 group. The optimal concentration of TP was measured by the MTT method. The expressions of TNF-α,IL-1β,IL-4,IL-10,VEGFA and VEGFR were detected by ELISA. The expressions of SDF-1,CXCR4 and VEGFA were detected by real-time quantitative PCR( RT-qPCR).The expressions of SDF-1,CXCR4,VEGFA and VEGFR were detected by Western blot. The expression levels of CD62 p,CD40 L and PDGFA were detected by immunofluorescence. MTT results showed that medium-dose TP had the strongest inhibitory effect on cells at24 h. The results of ELISA and PCR showed that TP inhibited mRNA expressions of IL-1β,TNF-α,VEGFA,VEGFR and SDF-1,CXCR4 and VEGFA. The results of Western blot indicated that TP inhibited SDF-1,CXCR4 and VEGFA,VEGFR protein expressions; immunofluorescence results indicate that TP can inhibit the expressions of CD62 p,CD40 L,PDGFA. TP may regulate platelet activation by down-regulating SDF-1,CXCR4,VEGFA and VEGFR mRNA expressions,thereby down-regulating IL-1β and TNF-αexpressions,and up-regulating the expressions of IL-4 and IL-10 cytokines.

Mobilization of hematopoietic progenitor cells for autologous transportation: consensus recommendations / Mobilização de células progenitoras hematopoéticas para transplante autólogo: recomendações de consenso

SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.

RESUMO Pacientes selecionados com certas neoplasias hematológicas e tumores sólidos têm o potencial de alcançar sobrevida de longo prazo com o transplante autólogo de células progenitoras hematopoéticas. A coleta dessas células no sangue periférico evita múltiplas aspirações de medula óssea, resulta em enxertia mais rápida, e permite o tratamento de pacientes com infiltração, fibrose ou hipocelularidade medular. Contudo, para o sucesso desse procedimento, é essencial mobilizar um número suficiente de células progenitoras da medula óssea para a circulação sanguínea. Por isso, um painel de especialistas brasileiros se reuniu com o objetivo de desenvolver recomendações para estratégias de mobilização adaptadas à realidade do sistema de saúde nacional, que pudessem contribuir para minimizar os riscos de falha, reduzir a toxicidade e melhorar a alocação de recursos financeiros.

Estudo do potencial antiproliferativo induzido por derivados 2-quinoxalinilidrazônicos em célulastumorais in vitro

As quinoxalinas são compostos heterocíclicos de baixo peso molecular, em sua maioria,sintéticos. Apresentam múltiplas atividades biológicas, o que justifica o crescente interesse daindústria farmacêutica. Entre essas atividades, pode-se citar a antineoplásica, antiinflamatória,antibacteriana, antiviral, antifúngica, antiparasitária, antidiabética, entre outras.O presente estudo avaliou os efeitos citotóxicos de três quinoxalinas sintéticas sobre aviabilidade de células tumorais. Por meio do método colorimétrico do MTT, as quinoxalinastestadas apresentaram CI50 decresente em função do tempo (24h, 48h e 72h). Dentre elas, aPJOV 56 destacou-se pela sua atividade antiproliferativa, com valores compreendidos entre0,82 a 7,35 µM (72 h) em células da linhagem HL-60 e HEPG2, respectivamente. Natentativa de caracterizar a ação citotóxica da molécula, a linhagem de câncer colorretal HCT-116 foi selecionada para tratamento com três concentrações (1,5, 3 e 6 µM) por 48h...

Consumo de carnes e aminas heterocíclicas como fatores de risco para câncer / Meat and heterocyclic amines intake as risk factors for cancer

Introdução. O alto consumo de carne, principalmente vermelha e processada, tem sido relacionado com aumento de risco de doenças crônicas, especialmente o câncer. Uma das explicações possíveis são os métodos de preparo culinário a altas temperaturas, que acarretam na formação aminas heterocíclicas. Estes compostos são detoxificados no nosso organismo, passando por um processo, no qual podem ser geradas espécies reativas, relacionadas ao estresse oxidativo e ao dano ao DNA. Entretanto, os indivíduos apresentam respostas diferentes à mesma exposição dietética, podendo ter diferentes níveis de risco ou benefício com a mesma ingestão de alimentos. O código genético individual pode ser uma das causas dessa variação interpessoal. Objetivo. Investigar a relação entre o consumo de carnes e aminas heterocíclicas com estresse oxidativo e dano no DNA, considerando polimorfismos genéticos, fatores demográficos e de estilo de vida em residentes do Município de São Paulo. Métodos. Foram utilizados dados dietéticos, genéticos, bioquímicos e estilo de vida de um estudo transversal com amostra probabilística de múltiplo estágio chamado Inquérito de Saúde de São Paulo (ISACapital). Os dados de carne e aminas heterocíclicas foram obtidos a partir de um recordatório alimentar de 24 horas e questionário sobre métodos de cocção e graus de cozimento das carnes. A extração do DNA ocorreu pelo método por sal e utilizou-se a técnica PCR em tempo real para determinação dos seguintes polimorfismos de nucleotídeo único: CYP1A1 (rs1048943), CYP1A2 (rs762551, rs35694136), CYP1B1 (rs1056836, rs10012), NAT2 (rs1208, rs1041983, rs1799929, rs1801280, rs1799931, rs1799930, rs1801279), NAT1 (rs4986782, rs5030839, rs56379106, rs56318881, rs6586714), SULT1A1 (rs928286), UGT1A9 (rs3832043), SOD2 (rs4880), CAT (rs7943316), GSTA1 (rs3957357), GSTP1 (rs1695), e deleção dos genes GSTM1 e GSTT1. Foram utilizados os biomarcadores malonaldeído (MDA) no plasma para estimar o estresse oxidativo e o 8-OHdG no plasma para estimar dano ao DNA. As associações foram examinadas por meio de modelos de regressão múltipla linear e logística ajustadas por sexo, idade, IMC, consumo de frutas e calorias, atividade física e fumo. Resultados. O consumo médio de aminas heterocíclicas foi de 437ng/dia e a carne de boi foi a que mais contribuiu para o consumo de aminas. Participantes que consumiram carne de boi grelhada muito bem passada apresentaram maiores concentrações de MDA do que os demais. Encontrou-se associação positiva entre consumo de aminas heterocíclicas com estresse oxidativo e dano ao DNA, isto é, indivíduos que consumiram maiores teores de aminas heterocíclicas apresentaram maiores chances de ter elevados concentrações de MDA (OR=1,17; P=0,04) e maiores concentrações de 8-OHdG (=1,62; P=0,04). Observou-se também que esta associação pode ser modificada pelas características genéticas individuais, sendo que polimorfismos nos genes das enzimas de detoxificação NAT2 e CYP1B1 interagiram com o consumo de aminas, diminuindo o estresse oxidativo. Conclusão. Verificou-se que o alto consumo de aminas heterocíclicas contribuiu para maiores níveis de estresse oxidativo e dano ao DNA independente de fatores demográficos e de estilo de vida, aumentando o risco de doenças crônicas. Observou-se também que esta relação pode ser alterada na presença de polimorfismos genéticos individuais

Introduction. The excessive meat intake, especially red and processed meat, has been linked to chronic diseases, especially cancer. One of the reasons for that is the cooking process at high temperatures that can form heterocyclic amines (HCA). During HCA metabolism, reactive species can be formed, which can cause oxidative stress and DNA damage. However, people can show different answers to the same food intake, increasing or decreasing the risk of diseases. The DNA code can be one of the causes of this between-person variations. Objective. To investigate the association between meat/heterocyclic amine intake with oxidative stress and DNA damage, considering polymorphism, demographic and life style factors among population of São Paulo city. Methods. Information on food intake, genetics, biochemical, and lifestyle was obtained from a representative, multistage probability-based cross-sectional study titled Health Survey for Sao Paulo (ISA-Capital). Meat and heterocyclic amine intake was estimated by a 24-hour dietary recall complemented by a detailed questionnaire with preferences of cooking methods and level of doneness for meats. The salt method was used for DNA extraction and real time PCR to identify the following single nucleotide polymorphisms: CYP1A1 (rs1048943), CYP1A2 (rs762551, rs35694136), CYP1B1 (rs1056836, rs10012), NAT2 (rs1208, rs1041983, rs1799929, rs1801280, rs1799931, rs1799930, rs1801279), NAT1 (rs4986782, rs5030839, rs56379106, rs56318881, rs6586714), SULT1A1 (rs928286), UGT1A9 (rs3832043), SOD2 (rs4880), CAT (rs7943316), GSTA1 (rs3957357), GSTP1 (rs1695), GSTM1 and GSTT1 (null or not). We used malondialdehyde (MDA) concentration in plasma to estimated oxidative stress, and 8-OHdG concentration in plasma to estimate DNA damage. Analyses were performed using multivariate logistic and linear regressions adjusted for smoking, sex, age, body mass index, energy intake, fruit intake, smoking and physical activity. Results. Mean HCA intake was 437ng/day and beef was the meat that contributed more to HCA. Participants who consumed grilled beef very well-done presented more MDA concentration than other participants. We found significant association between heterocyclic amine intake with oxidative stress and DNA damage. Participants who consumed high levels of heterocyclic amines showed higher odds to show high MDA concentration (OR=1.17; P=0.04) and high 8-OHdG concentration (=1.62; P=0.04). These associations could be modified by individual genetic characteristics. Polymorphisms in genes that codify NAT2 and CYP1B1 detoxification enzymes interacted with HCA intake, decreasing oxidative stress. Conclusions. The high heterocyclic amine intake contributed to increase oxidative stress independently of lifestyle and demographic factors, increasing risk of chronic diseases. These relationships can be modified by genetic polymorphisms

Exenatide promotes chemotactic migration of adipose-derived stem cells through SDF-1/CXCR-4/Rho GTPase pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of exenatide on chemotactic migration of adipose-derived stem cells (ADSCs) and confirm that Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 migration pathway.</p><p><b>METHODS</b>ADSCs were isolated, cultured, identified by flow cytometry, and induced to differentiate in vitro. RTCA xCELLigence system was used to analyze the effect of exenatide on ADSC proliferation. The effects of exenatide at different concentrations, AMD3100 (CXCR-4 antagonist), and CCG-1423 (Rho GTPase antagonist) on chemotactic migration of ADSCs were tested using Transwell assay. The expression of CXCR-4 in exenatide-treated ADSCs was measured by flow cytometry and Western blotting. Active Rho pull-down detection kit was used to detect the expression of Rho GTPase. Laser confocal microscopy was used to observe the formation of stress fibers in ADSCs with different treatments.</p><p><b>RESULTS</b>Exenatide treatment for 24 h had no significant effect on ADSC proliferation. Exenatide obviously promoted chemotactic migration of ADSCs in a concentration-dependent manner, and this effect was blocked by either AMD3100 or CCG-1423. Both flow cytometry and Western blotting showed that exenatide dose-dependently up-regulated CXCR-4 expression in ADSCs. Western blotting showed that the expression of Rho GTPase was related to SDF-1/CXCR-4 pathway, and laser confocal microscopy revealed that the formation of stress fibers in ADSCs was related to SDF-1/CXCR-4/ Rho GTPase pathway.</p><p><b>CONCLUSION</b>Exenatide promotes chemotactic migration of ADSCs, and Rho GTPase is the downstream effector protein of SDF-1/CXCR-4 pathway.</p>

Role of CXCR4/STAT3 in mesenchymal stromal cell-mediated drug resistance of acute leukemia cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the role of CXCR4/STAT3 in mesenchymal stromal cell (MSC)-mediated drug resistance of AML cells.</p><p><b>METHODS</b>AML cell lines U937 and KG1a and primary AML cells were co-cultured with MSC from bone marrow of healthy donors. The AML cell lines cultured alone were used as control. Apoptosis induced by mitoxantrone was measured by flow cytometry. Expression of CXCR4 and STAT3 protein were detected by Western blot. After incubated with STAT3 inhibitor Cucurbitacin I or CXCR4 antagonist AMD3100, the apoptosis of AML cells induced by mitoxantrone was evaluated.</p><p><b>RESULTS</b>Apoptosis of AML cells (U937 and KG1a) and primary AML cells induced by mitoxantrone significantly decreased in cocultured group than that of control group [U937 cells: (20.08±1.53)% vs (45.33 ± 1.03)% , P=0.004; KG1a cells: (25.60 ± 1.82)% vs (40.33 ± 3.29)% , P=0.020]. Expression of phosphorylated STAT3 and CXCR4 protein in AML cells were upregulated in cocultured group. After addition of Cucurbitacin I into the co-culture system, the apoptosis rate of primary AML cells significantly increased. Similar results of the apoptosis rates were also detected when the inhibitor of CXCR4 AMD3100 was added to overcome the stromal cell-mediated drug resistance. Besides, the expression of p-STAT3 in AML cells after incubated with AMD3100 decreased significantly.</p><p><b>CONCLUSIONS</b>AML cells cocultured with MSC leads to the up-regulation of phosphorylated STAT3 and CXCR4 proteins, which resulted in AML cells resistance to chemotherapeutic drugs. Therefore targeting STAT3 or CXCR4 could be a new therapeutic strategy of AML.</p>

High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen

OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer inhibitor (InSTI) that has been recently approved by the FDA to treat antiretroviral therapy-naive as well as treatment-experienced HIV-infected individuals, including those already exposed to the first-generation InSTI. Despite having a different mutational profile, some cross-resistance mutations may influence its susceptibility. The aim of this study was to evaluate the impact of a raltegravir-containing salvage regimen on dolutegravir activity. PATIENTS AND METHODS: Blood samples of 92 HIV-infected individuals with virological failure (two or more viral loads >50 copies/mL after 6 months of treatment) using raltegravir with optimized background therapy were sequenced and evaluated according to the Stanford University HIV Drug Resistance Database algorithm. RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations. At genotyping, patients with resistance to dolutegravir had viral load values closer to the highest previously documented viral load. CONCLUSIONS: Changes in viraemia during virological failure may indicate the evolution of raltegravir resistance and may predict the emergence of secondary mutations that are associated with a decrease in dolutegravir susceptibility. Early discontinuation of raltegravir from failing regimens might favour subsequent salvage with dolutegravir, but further studies are necessary to evaluate this issue.

Effects of SDF-1/CXCR4 signal pathway blockade by AMD3100 on the adhesion of leukemia cells to osteoblast niche and the drug resistance of leukemia cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the blocking effect of CXCR4 inhibitor AMD3100 on the adhesion of leukemia cells to osteoblast niche, and the reversal of multidrug resistance in leukemia cells.</p><p><b>METHODS</b>Mesenchymal stem cells (MSCs) from leukemia patients were planted on the bio-derived bone scaffolds and then induced into osteoblasts to establish the bio-osteoblast niche. The levels of SDF-1were tested with ELISA. The leukemia cell line MV4-11 cells with FLT3-ITD mutation were inoculated into the bio-osteoblast niche to build a three-dimensional co- culture system. The expression level of CXCR4, adhesion and apoptosis rates of leukemia cells were observed by flow cytometry after incubation with AMD3100 and Ara-C for 24 h and 48 h.</p><p><b>RESULTS</b>(1)The supernatant levels of SDF-1 in cultured osteoblast were (304 ± 18), (410 ± 28) and (396 ± 16) pg/ml on 7 th, 14 th and 21 th day, respectively. It reached the highest on 14 th day. The expression level of CXCR4 in cultured MV4-11 cells was (72 ± 16)%. (2)Adhesion rate of MV4-11 cells to osteoblast niche was (40.1 ± 8.1)% after AMD3100 treatment for 24 h, while that of control group was (65.6 ± 12.1)% (P<0.05). (3)The apoptosis rate of MV4-11 cells incubated with AMD3100 for 24 h was (5.6 ± 0.8)%, while that of control group was (2.5 ± 0.5)%. The apoptosis rates of AMD3100-induced MV4-11 cells were (10.0 ± 2.4)%, (17.8 ± 2.3)% and (25.1 ± 2.4)% after treatment with Ara-C at 0.02, 0.20, 2.00 mg/ml respectively and they were (6.7 ± 1.0)%, (10.3 ± 1.5)%, (16.2 ± 3.1)% respectively in AMD3100-noninduced control group, the difference was significant (P<0.05).</p><p><b>CONCLUSION</b>AMD3100 can block the interaction between osteoblasts niches and leukemia cells, and play an important role in the reversal of multidrug resistance in leukemia cells.</p>

Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model

OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.