Safety of G-CSF in patients with COVID-19 / 中国临床药理学与治疗学

COVID-19, a disease caused by SARSCoV-2 infection, has caused a global pandemic in a short time. The key immunopathological features of COVID-19 include lymphopenia, neutropenia, cytokine storm and related Immune damage to parenchymal organs such as lung. Granulocyte colony stimulating factor (G-CSF) can cause excessive inflammatory reaction, which may aggravate the condition of some patients. Therefore, it is controversial whether COVID-19 should be treated with G-CSF, and clinicians need to evaluate the effectiveness and safety of G-CSF according to the specific conditions of each patient.

Apheresis granulocyte collection and transfusion efficacy / 中国输血杂志

【Objective】 To analyze the safety of apheresis granulocyte(AG) collection from blood donors mobilized by G-CSF and apheresis granulocyte transfusion efficacy in patients. 【Methods】 The blood routine results, collection process and follow-up of blood donors mobilized by G-CSF before and after AG collection were collected to analyze the safety of AG collection, and the blood routine results, clinical symptom improvement and treatment outcome of patients before and after AG transfusion were collected to analyze the transfusion efficacy. 【Results】 A total of 27 blood donors donated 29 U AG, with collection time at (229±20)min, circulating blood volume at (9 890±1 107)mL, and the dosage of anticoagulant at (1 002±97)mL.Two blood donors had adverse reactions to blood donation, and the AG collection was carried out after treatment.After G-CSF mobilization, WBC increased significantly from (5.61±1.06) ×109/L to (22.85±5.23) ×109/L, while RBC, Hb, Hct and Plt showed no significant change.The blood routine returned to the level before G-CSF mobilization 1-2 days after blood donation.No physical discomfort occurred during the one week after blood donation.Four patients with granulocyte deficiency complicated with multidrug-resistant bacterial infection, who failed to respond to antibiotic treatment, were transfused with 29 U AG, with no adverse reactions and no obvious change in blood routine, but the infection symptoms were improved significantly judged from clinical manifestation, bacterial culture results, temperature monitoring and CT examination, suggesting that the AG infusion was effective.Among the 4 patients, 1 was cured and discharged, 1 gave up treatment, 1 died of sepsis, and 1 died of multiple organ failure. 【Conclusion】 It is safe to collect AG from blood donors mobilized by G-CSF through blood cell separator, and the AG products basically meet the national quality requirements and the treatment needs.Sustained high-dose AG transfusion has a significant effect on infection control in patients with agranulocytosis combined with refractory multidrug-resistant bacterial or fungal infection.

Effects of G-CSF on proliferation and fibrosis of lens epithelial cells / 西安交通大学学报(医学版)

【Objective】 In recent years, granulocyte colony stimulating growth factor (G-CSF) has been proved to be expressed in the posterior capsule of the lens of posterior capsular opacification (PCO), but its specific role remains unclear. The purpose of this study was to explore whether G-CSF plays a role in PCO. 【Methods】 First, human lens epithelial cells (HLEC-B3) were treated with different concentration of recombinant G-CSF protein and screened for effective appropriate concentration. Then, Western blotting was used to detect the effects of extracellular matrix (ECM) synthesis and epithelial mesenchymal transdifferentiation (EMT) marker genes after G-CSF treatment on HLEC-B3 cells. Finally, the effects of G-CSF treatment on the migration and invasion of HLEC-B3 cells were detected by scratch experiment and Transwell test. 【Results】 G-CSF at 80 μg/L could promote the proliferation of HLEC-B3 cells. After G-CSF was treated for 48 h, the expressions of EMT and ECM synthesis marker genes in HLEC-B3 cells were significantly upregulated with time. G-CSF could significantly promote HLEC-B3 cell invasion after 48 h induction. Similarly, G-CSF could also significantly induce cell migration compared to the CTRL group. 【Conclusion】 G-CSF can promote the proliferation, migration and invasion of HLEC-B3 cells, as well as EMT and ECM synthesis, which might be involved in the occurrence of PCO. Inhibiting the expression of G-CSF may be a new strategy for PCO prevention.

Study on anti-inflammatory effect of Salvia miltiorrhiza-Kushen herbpairs extract based on network pharmacology / 中国药理学通报

Aim To predict the potential targets of Salvia miltiorrhiza- Kushen herb pairs extracts (SK) and explore its anti-inflammatory effect on modelsbased on network pharmacology, so as to provide the research foundation of both new drugs and anti-inflammatory mechanism. Methods Network pharmacology was used to predict the potential anti-inflammatory targets of SK. Ear edema model was used to study the anti-in- flammatoiy effects of SK. Luminex liquid-phase chip analysis technology was used to observethe changes in secretion of pro-inflammatory cytokines in peripheral serumafter transdermal administration in mice by SK. Intraperitoneal injection of Evans blue experiment was used to simulate the exudation of inflammatory factors, and the effect of SK on capillary permeability in mice- was explored. Results Network pharmacology was used to predict that the anti-inflammatory effect of SK- was mainly related to immune-related processes and VEGF signaling pathways, unravelingthe relationship between the anti-inflammatory mechanismand the decrease of pro-inflammatory factors and vascular permea- bility. Conclusions The experiments verify that the results are the same as the prediction by network pharmacology. The anti-inflammatory effect involves decline the IL-6 levels, granulocyte colony-stimulating factor( G-CSF) levels and vascular permeability in the STAT3 pathway. Asthemain components of SK, tanshi- none, matrine and oxymatrine are linked to anti-in- flammatory effects.

Granulocyte colony stimulating factor in COS-IUI cycles

Background: An unresolved assisted reproductive technique problem is the unresponsive, thin endometrium. Approximately 0.6%-0.8% of patients do not reach the minimum thickness. Using endometrial co culture, G-CSF>130pg/mL was associated with significantly improved pregnancy rate in ART cycles. This is a retrospective study that included all unexplained infertility cycles with controlled ovulation stimulation –IUI protocols. Aim was to note the effects of G-CSF on thin endometrium and pregnancy rate in G-CSF administered COS-IUI cycles.Methods: This study was done in the IVF department of Dr D Y Patil University, Navi Mumbai, India. Thin endometrium was defined as ET<7mm on transvaginal ultrasound. Clomiphene citrate was used for ovulation induction in strengths of 100mg or 50mg on day 2 of their cycle based on the antral follicle count. Trigger used was injection 10,000µg urinary hCG. On the same day when the trigger injection was given, 300 units G-CSF was instilled into the uterus. Post 36 hours IUI was done under aseptic precautions .After 16 days β-hCG levels were done to determine whether there is a pregnancy.Results: In present study,200 COS-IUI cycles were analysed.50 cycles showed a thin endometrium and in them G-CSF was used. The chemical pregnancy rates was 32%, the intrauterine pregnancy rate was 28%, ectopic pregnancy rate was 4%.Conclusions: Present study concluded that G-CSF increases ET significantly in COS-IUI cycles in the event of thin endometrium. In view of small cohort size further larger randomized controlled trials may be required  to substantiate the above conclusions.

The therapeutic effect of G-CSF-mobilized autologous stem cells on radiation pulmonary injury in mice / 中华放射医学与防护杂志

Objective To investigate the effects of G-CSF-mobilized autologous stem cells in the prevention of radiation pulmonary injury.Methods Mice were divided into control group,irradiation group and treatment group.Mouse model of pulmonary fibrosis was established by exposing chest to a single dose of 14 Gy.Animals in the treatment group received recombinant human G-CSF (250 μg/kg daily for 5 d) before the irradiation in order to mobilize autologous stem cells in vivo.The general condition and mortality were documented after radiation injury.The pathological study with histological scoring,Masson staining and Sirius red staining with polarized light analysis were used to identify lung injury and the potential benefit of stem cell mobilization.Results Local chest irradiation of a single dose of 14 Gy was a suitable dose to create radiation-induced pulmonary fibrosis in mice.The death rate was 37.5％,which mainly happened around 11 weeks after injury.In contrast,all of the animals in G-CSF treated group survived.The ratio of lung to body mass was significantly increased in both irradiation group and treatment group (F =23.20,P＜0.05) around 3 months after the injury,with a higher ratio in irradiation group than that in treatment group (P＜0.05).Histological scoring for alveolar inflammation at 3 months after injury revealed statistically significant difference in irradiation group and treatment group compared with control group (F=11.93,P＜ 0.05).At this time point,the pathological observation showed lung tissue degeneration and necrosis with alveolitis and interstitial inflammation,as well as fibroblasts proliferation and focal collagen deposition in alveolar septa.At 4 month after the injury,the inflammation ininterstitial tissue was receded,but fibrosis and collagen deposition were significantly increased.In addition,at 3 and 4 months afterinjury,the pulmonary fibrosis was aggravated in irradiation group (F=28.73,16.85,P＜0.05),and significantly alleviated in the treatment group (P＜0.05).The similar results were confirmed in collagen content analysis (IOD) by Sirius red staining and image analysis (F =17.70,17.79,P＜ 0.05).Conclusions Autologous mobilization of stem cells could prevent the death of radiation-injured animals possibly by alleviating early lung injury and interstitial inflammation as well as the late pulmonary fibrosis,suggesting a therapeutic potential of autologous stem cell mobilization in radiation pulmonary fibrosis.

Tratamiento complementario de heridas crónicas con factor de crecimiento estimulante de colonias de granulocitos. A propósito de dos casos clínicos / Granulocyte Colony-Stimulating Growth Factor complementary treatment in chronic wounds. Report of two cases / Tratamento complementar de feridas crônicas com colônias de granulócitos estimulantes do fator de crescimento. Cerca de dois casos clínicos

RESUMEN: Introducción: Independientemente de su etiología, las heridas crónicas, representan un desafío terapéutico debido a que muchas veces son refractarias a tratamientos convencionales. Es por este motivo que en los últimos años se han desarrollado de forma creciente estrategias complementarias en el área de la medicina regenerativa, como: terapias con células madre, ingeniería de tejidos, plasma rico en plaquetas y factores de crecimiento aplicados en las heridas crónicas. Dichas terapias complementarias han mostrado ciertos beneficios en la cicatrización de heridas complejas. Materiales y métodos: Se presentan dos casos clínicos de pacientes con heridas crónicas de diferente etiología, refractarias al tratamiento con cura avanzada de heridas, las cuales recibieron de forma complementaria factor estimulante de colonias de granulocitos (G-CSF; Filgen®). Se realizaron inyecciones locales de G-CSF a una dosis de 300 mcg/ml en piel peri úlcera en forma semanal completando dos series de cuatro inyecciones cada una. Resultados. Ambos casos presentaron una reducción en el área de las mismas alcanzándose la cicatrización total en un paciente y una reducción del 37% en el otro luego de dos series. El procedimiento fue bien tolerado y no se reportaron efectos adversos relacionados al mismo. Conclusiones: Los resultados obtenidos en estos pacientes mostraron beneficios en la cicatrización con la aplicación del G-CSF. Se requieren de ensayos clínicos controlados que permitan establecer el rol de dicho factor en el tratamiento de las mismas. Por este motivo nuestro grupo de trabajo se encuentra desarrollando un protocolo que permita evaluar este aspecto.

ABSTRACT: Introduction: Regardless of their etiology, chronic wounds, represent a therapeutic challenge because they are often refractory to conventional treatments. Due to this observation, in the last few years, new complementary strategies have emerged in the area of regenerative medicine, including stem cell therapeutics, tissue engineering, platelet rich plasma, and growth factors applied to chronic wounds. These complementary therapies have shown certain benefits in healing of complex wounds. Materials and methods: We present two clinical cases of patients with chronic wounds of different etiology, refractory to advanced and conventional wound treatments, which received complementary granulocyte colony-stimulating growth factor (G-CSF; Filgen®). Local injections with G-CSF were administered weekly in periulcer skin at a dose of 300 mcg/ml, completing two series of four injections each. Results: Both cases showeda reduction in their areas, reaching to total healing inone patient, and a reduction of 37% in the other one after two series of treatment. The procedure was well tolerated and no adverse effects were detected. Conclusions: The results obtained with these patients showed a benefit in cicatrization with the administration of G-CSF. Controlled clinical trials are needed to establish the role of G-CSF in these wounds. Thus, our group is developing a protocol to evaluate this aspect.

RESUMO: Introdução: Independentemente da sua etiologia, as feridas crônicas representam um desafio terapêutico porque muitas vezes são refratárias aos tratamentos convencionais. É por esta razão que nos últimos anos foram desenvolvidas estratégias complementares na área da medicina regenerativa, tais como: terapias de células estaminais, engenharia de tecidos, plasma rico em plaquetas e fatores de crescimento aplicados a feridas crônicas. Tais terapias complementares mostraram certos benefícios na cicatrização de feridas complexas. Materiais e métodos: Dois casos de pacientes com feridas crónicas de diferentes etiologias, refractárias ao tratamento com a cura da ferida avançado, que receberam complementaria factor estimulante forma de colónias de granulócitos (Filgen® FEC-G) presente. As injeções locais de G-CSF foram feitas a uma dose de 300 mcg / ml na pele peri úlcera, semanalmente, completando duas séries de quatro injeções cada. Resultados: Ambos os casos mostraram uma redução na área do mesmo atingindo a cicatrização total em um paciente e uma redução de 37% no outro após duas séries. O procedimento foi bem tolerado e nenhum efeito adverso relacionado a ele foi relatado. Conclusões: Os resultados obtidos nestes pacientes mostraram benefícios na cura com a aplicação de G-CSF. Ensaios clínicos controlados são necessários para estabelecer o papel desse fator no tratamento deles. Por esse motivo, nosso grupo de trabalho está desenvolvendo um protocolo que nos permite avaliar esse aspecto.

A Case of G-CSF-producing Duodenal Cancer That Steroid Was Remarkably Effective to Alleviate Symptoms at the End of Life

Introduction: G-CSF producing tumors often cause various symptoms at the end of life, such as fever, fatigue, and fluid retention as a result of high cytokine status. Case: The patient was an 80-year-old woman. She was referred to our hospital because of anorexia and urine volume reduction. After a detailed examination, she was diagnosed with duodenal cancer. Although she decided not to receive anticancer treatment because of her old age and poor general condition, she felt a great distress with abdominal distension by large ascites. Furthermore, peripheral blood smear examination showed remarkably increased levels of normal neutrophils. We suspected G-CSF producing tumor and, hence, dexamethasone administration was initiated to suppress cytokine release. As a result, renal dysfunction and urine volume were improved, and ascites accumulation was not observed again since initial paracentesis. The number of neutrophils also declined, and the patient was in a good condition, even though it lasted for a short time. Conclusion: In patients with high cytokine status caused by G-CSF producing tumor, steroids may be useful for pain relief.

Serial Changes of Cytokines in Children with Cerebral Palsy Who Received Intravenous Granulocyte-colony Stimulating Factor Followed by Autologous Mobilized Peripheral Blood Mononuclear Cells

BACKGROUND: This study was performed to assess serial cytokine changes and their clinical impact in children with cerebral palsy (CP) who received granulocyte-colony stimulating factor (G-CSF) followed by infusion of autologous mobilized peripheral blood mononuclear cells (mPBMCs). METHODS: Peripheral blood (PB) samples were collected from 16 CP children at enrollment, and 1 month and 7 months after G-CSF infusion as well as at the end of the study. Cytokine levels were measured by enzyme-linked immunosorbent assays with plasma samples. RESULTS: There were no significant differences in cytokine levels between the mPBMC and placebo groups over 6 months. However, when clinical responders and non-responders were compared, interleukin (IL)-6 (P = 0.050) as well as G-CSF (P = 0.010) were higher in the responders than the non-responders at 1 month, while brain-derived neurotrophic factor (BDNF) (P = 0.030) and insulin-like growth factor (IGF)-1 (P = 0.001) were lower. In addition, BDNF was higher at baseline in the responders than the non-responders (P = 0.030). CONCLUSION: The changes of G-CSF itself, as well as G-CSF-induced cytokines such as IL-6, may be associated with the clinical improvement of neurologic functions. The G-CSF-induced changes of IL-6, BDNF and IGF-1, and BDNF levels before treatment, could be used as prognostic factors in G-CSF trials in CP children.

Terapia com células-tronco mesenquimais geneticamente modificadas para superexpressão de G6GSF e IGF-1 na doença de chagas crônica experimental / Therapy with genetically modified mesenchymal stem cells for overexpression of G6GSF and IGF-1 in experimental chronic chagasic disease

INTRODUÇÃO: A doença de Chagas é uma doença parasitária causada pelo Trypanosoma cruzi, a qual representa uma das principais causas de morbimortalidade na América Latina. As intervenções terapêuticas existentes não são totalmente eficazes, sendo o transplante cardíaco a única alternativa para os pacientes com cardiopatia chagásica crônica (CCC) grave. Neste sentido, a ausência de terapias capazes de atuar diretamente sobre os determinantes fisiopatológicos da doença torna necessária a identificação de novas abordagens terapêuticas. Estudos previamente realizados pelo nosso grupo mostraram que a utilização de célulastronco obtidas da medula óssea e de outras fontes teve efeitos benéficos no tratamento da CCC experimental. A possibilidade de potencializar os efeitos parácrinos das células-tronco através de modificação genética tem sido alvo de investigações científicas. OBJETIVO: Avaliar os efeitos da terapia com células-tronco mesenquimais (CTMs) da medula óssea, modificadas geneticamente para superexpressar o fator estimulador de colônias de granulócitos (hG-CSF) ou o fator de crescimento semelhante à insulina 1 (hIGF-1) em um modelo experimental de CCC. MATERIAL E MÉTODOS: Camundongos C57BL/6 foram infectados com 1000 tripomastigotas da cepa Colombiana de T. cruzi e, após seis meses de infecção, foram tratados com CTM, CTM-G-CSF, ou CTM-IGF-1. Grupos de animais não infectados ou infectados tratados com salina (veículo) foram utilizados como controles. Todos os animais foram eutanasiados sob anestesia após dois meses de tratamento para análises histopatológicas e morfométricas do coração ou músculo esquelético, bem como para avaliação da expressão de citocinas inflamatórias. RESULTADOS: As secções de corações de camundongos dos grupos tratados com CTM, CTM-GCSF ou CTM-IGF-1 apresentaram redução significativa do número de células inflamatórias e do percentual de fibrose em comparação aos animais chagásicos tratados com salina, sendo esta diferença mais evidente no grupo que foi tratado com células-tronco que superexpressam o G-CSF. Além disto, a terapia com CTM-G-CSF induziu a mobilização de células imunomoduladoras para o coração, tais como células supressoras de origem mielóide (MDSC) e células T regulatórias Foxp3+ que expressam IL-10. A avaliação da expressão gênica das citocinas inflamatórias no tecido cardíaco mostrou um aumento das citocinas inflamatórias em animais chagásicos crônicos quando comparados aos controles não infectados, sendo a maioria delas moduladas de forma significativa nos grupos que foram tratados com CTM ou CTM-G-CSF. Apesar da terapia utilizando CTM-IGF-1 não ter apresentado benefício adicional ao tecido cardíaco comparado ao grupo que foi tratado com CTM não modificadas, foi observado um efeito regenerativo desta terapia no músculo esquelético dos animais, resultando em um aumento de fibras musculares esqueléticas 60 dias após o tratamento. CONCLUSÃO: Nossos resultados demonstram que o tratamento com CTM da medula óssea que superexpressam hG-CSF ou hIGF-1 potencializou o efeito terapêutico das CTMs através de ações imunomoduladoras e pró-regenerativas no coração e músculo esquelético de camundongos cronicamente infectados por T. cruzi. Desse modo, a modificação genética de CTMs para superexpressão de fatores com potencial terapêutico representa uma estratégia promissora para o desenvolvimento de novas terapias para a cardiomiopatia chagásica crônica

INTRODUCTION: Chagas' disease is a parasitic disease caused by Trypanosoma cruzi, which is one of the main causes of cardiovascular morbidity and mortality in Latin America. Existing therapeutic interventions are not fully effective, and heart transplantation is the only alternative for patients with severe chronic Chagas' heart disease. In this sense, the absence of therapies capable of acting directly on the pathophysiological determinants of the disease demonstrates the necessity of identifying new therapeutic approaches. Studies previously conducted by our group demonstrated that the use of stem cells obtained from bone marrow and other sources had beneficial effects in the treatment of experimental chagas disease. Additionally, the possibility of enhancing stem cell paracrine effects through genetic modification has been the subject of scientific investigations. OBJECTIVE: To evaluate the effects of genetically modified mesenchymal stem cell therapy to overexpress granulocyte colony stimulating factor (hG-CSF) or insulin-like growth factor 1 (hIGF-1) in an experimental model of Chagas disease. MATERIAL AND METHODS: C57BL/6 mice were infected with 1000 trypomastigotes from the Colombian strain of T. cruzi and, after six months of infection, were treated with CTM, CTM-G-CSF, or CTM-IGF-1. Groups of uninfected or infected animals treated with saline (vehicle) were used as controls. All animals were euthanized under anesthesia after two months of treatment for histopathological and morphometric analysis of the heart or skeletal muscle, as well as for evaluation of inflammatory cytokine expression. RESULTS: Mouse heart sections from groups treated with CTM, CTM-GCSF or CTM-IGF-1 showed a significant reduction in the number of inflammatory cells and the percentage of fibrosis when compared to chagasic animals treated with saline.This difference was more evident in the group that was treated with stem cells overexpressing G-CSF. In addition, CTM-G-CSF therapy induced mobilization of immunomodulatory cells to the heart, including myeloid suppressor cells (MDSC) and Foxp3 + regulatory T cells expressing IL-10. Expression of inflammatory cytokine genes in cardiac tissue revealed an increase in inflammatory cytokines in chronic chagasic animals when compared to uninfected controls, where most cytokines were significantly modulated in groups treated with CTM or CTM-G-CSF. Although CTM-IGF-1 therapy demonstrated no additional benefit to cardiac tissue when compared to the group treated with unmodified CTM, a regenerative effect of this therapy was observed in chagasic mice skeletal muscle, resulting in an increase in skeletal muscle fibers 60 days after treatment. CONCLUSION: Our results demonstrate that bone marrow derived CTM treatment overexpressing hG-CSF or hIGF-1 enhanced the therapeutic effects of MSCs through immunomodulation and proregenerative actions in the heart and skeletal muscle of mice chronically infected wthT. cruzi. Thus, the genetic modification of CTMs for overexpression of factors with therapeutic potential represents a promising strategy for the development of new therapies for chronic chagasic cardiomyopathy

Changes of Neutrophil Morphological Parameters in Peripheral Blood of Patients with Solid Tumor Treated with Granulocyte Colony Stimulating Factor / 现代检验医学杂志

Objective To study neutral particle particle(NEUT-X)change in the solid tumor patients with chemotherapy by granulocyte colony-stimulating factor(G-CSF).Methods Chose that 52 cases of cancer chemotherapy with G-CSF(study group),32 cases of cancer chemotherapy patients without G-CSF(study control group)and 50 cases of healthy(healthy control group).The automatic hematology analyzer Sysmex XE-2100 were been examined the peripheral blood routine and collected the data which wes the morphological parameters of peripheral white blood cell.The changes of neutrophil N-X pa-rameters during chemotherapy were analyzed,and the clinical infection fever rates of three groups were collected to reveal the relationship between leukocyte morphological parameters and body resistance.Results In the study group,study control group and healthy control group,the NEUT-X was 1 324(890.2,1 358.0),1 440(1 397.3,1 466.3)and 1 329(1 295.1, 1 359.4),and the difference was statistically significant between the three groups(F=10.778,P=0.002).In study group, the count of WBC before and after G-CSF was 0.99(0.22,1.75)×109/L and 7.53(1.00,14.05)×109/L respitively and there was the significant difference(Z=-2.395,P=0.005).In study group patients the NEUT-X was 1 382(1 323.6,1 440.4)and 1 324(890.2,1 358.0)respectively and there was a significant difference(Z=-2.832,P=0.004).Between the study group and the study control group,there were 23/52 cases and 4/32 cases infection in patients with fever case(Z=9.14,P=0.002).Conclusion By G-CSF the leukocyte counts increased in patients with chemotherapy,and reduced neu-trophil NEUT-X parameters,and the infection rate was higher than the non G-CSF patients.The neutrophil granularity will be useful for evaluating of patients with chemotherapy for solid tumor immunity.

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.

A intervenção educativa do enfermeiro no uso domiciliar do fator estimulador de colônias granulocítica (G-CSF): relato de experiência / The educational intervention of nurses in home use of granulocyte colony stimulating factor (G - CSF): experience report

Relatar a experiência oriunda da vivência de uma enfermeira assistencial, desenvolvidas no setor de quimioterapia infantil com os familiares de crianças em tratamento quimioterápico no âmbito ambulatorial e que fazem uso do G-CSF em domicilio. MÉTODO: estudo descritivo, tipo relato de experiência, realizado no serviço de quimioterapia infantil de um hospital público de referência no atendimento oncológico e de ensino e pesquisa do RJ Alicerçou-se na vivência de acompanhar os familiares de criança em tratamento quimioterápico que cursam com neutropenia pós-quimioterapia e necessitam do G-CSF, e busca promover o acolhimento deste familiar através da educação a partir da compreensão do sofrimento vivenciado pelo familiar da criança com câncer no processo do cuidado em domicilio. CONCLUSÃO: o enfermeiro que assiste á criança em tratamento oncológico deve ser capacitado, ter sensibilidade e compreender que a sua assistência é estendida a este familiar mediante as suas necessidades de acolhimento durante as diversas fases do tratamento da criança...

To report the experience comes from the experience of an assistant nurse, developed in the sector of chemotherapy playground with family members of children in chemotherapeutic treatment under ambulatory and who make use of the G-CSF in their formative years. Method: Descriptive study experience report, accomplished in the service of chemotherapy playground of a public hospital of reference in Oncological care and of teaching and research of RJ. Supported in the experience of accompany family of a child in chemotherapeutic treatment coursing with neutropenia post-chemotherapy and need of G-CSF, and seeks to promote the acceptance of this family through education from the understanding of the suffering experienced by the family of the child with cancer in the process of care in the home. Conclusion: the nurse who assists will be child in oncologic treatment must be trained, have sensitivity and understand that its assistance is extended to this family through their host needs during the various stages of the treatment of the child...

Presentar la experiencia derivada de una enfermera clínica, desarrollada en el sector de la quimioterapia infancia con las familias de los niños que reciben quimioterapia en forma ambulatoria y hacer uso de G-CSF en domicilio. Métodos: Estudio descriptivo, informe de la experiencia, que se celebró en el servicio de la quimioterapia de los nines de un hospital público de referencia en el tratamiento del cáncer y de la ensenanza y la investigación de RJ Sus fundamentos en la experiencia de acompanar a la familia del niño en concomitante quimioterapia, con neutropenia después de la quimioterapia y la necesidad de que el G-CSF, y busca promover la acogida de esta família a través de la educación a partir de la comprensión del sufrimiento experimentado por la familia del niño con proceso de atención del cáncer en el hogar. CONCLUSION: La enfermera que ayude aios nines en el tratamiento del cáncer debe ser calificado, ser sensibles y entienden que su asistencia se extiende a esta familia a través de sus necesidades de alojamiento durante las diversas etapas del tratamiento del niño...

Expression of NAP in patients with acute myeloid leukemia / 实用医学杂志

Objective To investigate the expression of NAP in patients with acute myeloid leukemia (AML). Methods Expression of NAP of peripheral blood was assessed by flow cytometry. The serum levels of G-CSF, NE and IL-18 in 53 patients with AML and 50 healthy controls were examined by ELISA. Results The expression of NAP in AML patients [1 159(563 ~ 2 033)AB/c] was decreased than that of healthy controls [1 862 (1 345 ~ 2 382)AB/c], (P < 0.05). The serum levels of G-CSF, NE and IL-8 from AML patients [34.36 (25.17 ~ 47.24) ng/L, 397.56 (324.63 ~ 563.84) pg/mL, 585.34 (403.61 ~ 866.54) pg/mL] were significantly lower than those of healthy controls[54.52(46.27 ~ 77.14) ng/L, 689.74(496.78 ~ 899.14) pg/mL, 832.36(625.17 ~ 998.24) pg/mL] (P < 0.05). The expression of NAP in AML patients was positively correlated with the serum level of G-CSF (r = 0.621, P = 0.007). Conclusions The decreased expression of NAP, G-CSF, NE and IL-8 in the peripheral blood with AML could speculated that neutrophils immune function in patients with AML was restrained.

Ação educativa do enfermeiro no cuidado domiciliar de adolescentes e crianças: uso do fator estimulador de crescimento de colônia granulocítica (G-CSF) ­ uma perspectiva fenomenológica / Nursing education in the home care of adolescents and children: use of granulocytic colony growth stimulating factor (G-CSF) - a phenomenological perspective

Problema: Atualmente o câncer infantil representa a segunda causa de morte na faixa etária de 5 a 19 anos, ultrapassado apenas pelos óbitos provocados por causas externas. E, a partir do diagnóstico, traça-se uma das propostas de tratamento, a terapêutica com os agentes antineoplásicos, conhecidos como quimioterápicos, os quais são responsáveis pelo longo período de internação, tendo em vista que um dos efeitos adversos desta terapêutica com maior incidência é a neutropenia pós-quimioterapia. Tal condição representada pela contagem de neutrófilos inferior a 1500/m3 torna necessário o uso de moduladores de resposta muitas vezes em domicílio. Objetivo: Este estudo tem como objetivo construir uma ação educativa durante a utilização em domicílio do fator estimulador de colônias granulocíticas (G-CSF), pelo paciente e/ou familiar, buscando conhecer o significado desta ação educativa a ser construída em conjunto com os familiares, considerando e respeitando o conhecimento e saber emanado por eles, em todo o processo holístico de saúde onde o indivíduo apresenta necessidades interligadas ao meio que o cerca. Método: É um estudo de natureza qualitativa, tipo descritivo com apropriação do método fenomenológico na percepção de Maurice Merleau Ponty, e a teoria transpessoal de Jean Watson e teve como cenário o centro de quimioterapia infantil do Instituto Nacional de Câncer, que é uma Instituição Pública Federal de referência na área oncológica, e obteve aprovação no CEP em 22/12/2015n° do CAAE-51715515.500005243 e no CEP da instituição coparticipante em 07/01/2016 n0 do CAAE-51715515.5.3001.5274. O estudo foi desenvolvido em conformidade com os princípios éticos estabelecidos na Resolução do Conselho Nacional de Saúde (CNS) 466/12. Resultado: A coleta de dados ocorreu no serviço de quimioterapia infantil por meio de entrevista com participação de dezoito familiares. As entrevistas foram transcritas na integra com apropriação do método de Giorgi e após analise a luz da fenomenologia da Percepção de Maurice Merleau-Ponty originou-se a formação de quatro categorias: Categoria 1-O impacto do diagnóstico de câncer na perspectiva do familiar; Categoria 2-O significado do câncer e tratamento na percepção do familiar; Categoria 3-A importância da espiritualidade na percepção do familiar da criança com câncer; 4-O significado do cuidado domiciliar na perspectiva do familiar. Considerações finais: Durante o decorrer deste estudo percorreu-se um caminho direcionado ao cuidado, tanto ao cuidador quanto do ser a ser cuidado com o objetivo de compreender e auxiliar os familiares no processo do cuidar a partir da percepção da experiência vivenciada por estes em um contexto familiar. Tais propósitos incluíram o respeito e valorização do conhecimento e das experiências desses familiares, incluindo suas crenças, cultura, e hábitos sociais. E, neste contexto é de extrema importância que o enfermeiro vivencie a experiência a partir da percepção do sujeito deste estudo, considerando os conceitos humanísticos, visando almejar uma assistência cada vez mais qualificada e de excelência, o que propiciou a construção de uma tecnologia educacional (cartilha educativa), no que se refere ao uso em domicilio do fator estimulador de crescimento de colônias de granulócitos

Problem: Currently, childhood cancer represents the second cause of death in the age group of 5 to 19 years, surpassed only by deaths caused by external causes. From the diagnosis, one of the treatment proposals is the treatment with antineoplastic agents, known as chemotherapeutic agents, which are responsible for the long period of hospitalization, considering that neutropenia is one of the adverse effects of this therapy with a higher incidence after chemotherapy. That condition, represented by the neutrophil count below 1500 / m3 makes it necessary to use response modulators often at home. Objective: This study aimed to construct an educational action during the use of the granulocytic colony-stimulating factor (G-CSF), by the patient and / or family member at home. It seeks to know the meaning of this educational action built together with the family, considering and respecting the knowledge and knowledge emanated by them, throughout the holistic process of health where the individual present needs interconnected to the environment that surrounds him. Method: It is a descriptive qualitative study, based on the phenomenological method from the perspective of Maurice Merleau Ponty, and the transpersonal theory of Jean Watson. It had as setting the child chemotherapy center of the National Cancer Institute, which is a public federal hospital, specialized in oncology area, and obtained approval in the CEP on 12/22/2015 under protocol number CAAE51715515.500005243 and in the CEP of the participating Institution on 07/01/2016 under protocol number CAAE-51715515.5.3001.5274. The study was developed in conformity with the ethical principles set out in National Health Council (CNS) Resolution No.466/12. Results: Data collection took place in the infant chemotherapy service through an interview with the participation of eighteen relatives. We transcribed the interviews in full, with appropriation of the Giorgi method, followed by analysis under the perspective of the phenomenology of Perception by Maurice Merleau Ponty. Then, four categories originated category 1. The impact of the cancer diagnosis from the family perspective; category; 2. The meaning of the cancer and treatment under the perception of the family member; category 3. The importance of the spirituality under the perception of the family member of the child with cancer; -the meaning of home care from the perspective of the family member. Final Considerations. During the development of this study, we went through a path directed to care that reached both the caregiver and the being to be cared for with the objective of understanding and helping the family in the care process from the perception of experiences lived by them in a family context. Such purposes included the respect and valorization of the knowledge and experiences of these relatives, including their beliefs, culture, and social habits. And in this context, it is extremely important that nurses live the experience from the perception of the subject of this study, considering the humanistic concepts, aiming for an increasingly qualified and excellent assistance, which has enabled the construction process of an educational technology (educational leaflet) as regards the use at home of granulocytes colony stimulating factor

Problema: En la actualidad el cáncer infantil es la segunda causa de muerte en el grupo de edad de 5-19 años sólo superada por las muertes provocadas por causas externas. Y, desde el diagnóstico, se expone una de las propuestas de tratamiento, la terapéutica con agentes antineoplásicos, conocidos como la quimioterapia, los cuales son responsables por el largo período de hospitalización, dado que algunos de los efectos adversos de este tratamiento con mayor incidencia es la neutropenia pos quimioterapia. Tal condición representada por un conteo de neutrófilos inferior a 1.500 / m3 hace que sea necesario el uso de moduladores de la respuesta muchas veces en el domicilio. Objetivo: Este estudio tiene como objetivo construir una actividad educativa durante el uso del estimulador de colonias de factor de granulocitos (G-CSF), el paciente y / o familia en uso en el familiar, buscando conocer el significado de esta actividad educativa que se construirá en conjunto con el familia, teniendo en cuenta y respetando los conocimientos y experiencia que emana de ellos durante todo el proceso holístico de salud donde el individuo presenta necesidades interrelacionadas con el medio que lo rodea. Método: Se trata de un estudio cualitativo, descriptivo, con la apropiación del método fenomenológico en la percepción de Maurice Merleau-Ponty, y la teoría transpersonal Jean Watson y se realizó en el centro de la quimioterapia de los niños del Instituto Nacional del Cáncer, que es una institución pública Federal referencia en oncología, con la aprobación en el CEP Coordinador 22/12/2015 Nº de CAAE-51715515.500005243 y CEP de la institución copartícipe en el CAAE 01/07/2016 N.51715515.5.3001.5274. Se realizó a partir de los principios éticos que implican la investigación en seres humanos. Resultados: Los datos fueron recolectados en el servicio de quimioterapia infantil a través de entrevistas con la participación de dieciocho familiares. Las entrevistas se transcribieron enteras con apropiación del método de Giorgi y después del análisis a la luz de la fenomenología de Maurice Merleau-Ponty se originó la formación de cuatro categorías: Categoría 1-El impacto del diagnóstico de cáncer en la perspectiva de la familia; Categoría 2-El significado del cáncer y el tratamiento en la percepción de la familia; Categoría 3-La importancia de la espiritualidad en la percepción de la familia de los niños con cáncer; 4-El significado de la atención domiciliaria en perspectiva familiar. Consideraciones finales: En el transcurso del estudio se ha recorrido un camino dirigido a la atención, para llegar tanto al cuidador como al ser humano que debe ser cuidado con el fin de comprender y ayudar a la familia en el proceso de atención a de la percepción de la experiencia vivida por ellos en un contexto familiar, respetando y valorando los conocimientos y experiencias de vida de estas familias, con sus creencias, la cultura y los hábitos sociales y, en este contexto, es extremadamente importante que las enfermeras experimentan la experiencia a partir de la percepción del sujeto de este estudio, teniendo en cuenta los conceptos humanísticos, buscando una asistencia cada vez más cualificada y de excelencia, que propició la construcción de una tecnología educativa (cartilla educativa) en lo que respecta al uso en domicilio del factor de crecimiento de colonias de granulocitos

Evaluation of the Hematologic Profile of Patients Undergoing Chemothera • who Make use of Hemato • oietic Rescue Workers.

Cytotoxic chemotherapy is directly linked hematologic changes during your anticancer treatment. The hematopoietic rescue agents can be used as supportive care for patients with anemia or neutropenia induced by cytotoxic chemotherapy. This study aimed to evaluate the blood count of patients undergoing chemotherapy and who made use of hematopoietic rescue workers, evaluating hematological changes induced by cytotoxic chemotherapy. This was a retrospective, descriptive and analytical study of the medical records of 36 patients undergoing chemotherapy and who used hematopoietic rescue workers at some time in their anticancer treatment in a High Complexity in Oncology Center. Of the patients included in the study population, 61% are female, and the average age of these is 57,25 years (SD ± 10,84), the most prevalent cancer among patients was the breast (48%), hematological used rescue agent is Filgrastim (53%), Erythropoietin (33%) and Erythropoietin and Filgrastim (144 The pharmacological class used in anticancer therapy in prevalence is the antimitotic taxoids and associations, representing 53% of the study population. The results of this study, as well as data from the scientific literature, demonstrate the importance of the use of hematopoietic rescue agents in chemotherapy protocols, due to the proliferative effect / therapeutic these growth factors, which reduce side effects of chemotherapy cytotoxic, giving cancer patients a better quality of life to follow your anticancer treatment, and thus increase the chance of cure.

Effect of G-CSF and TPO on HIBD in neonatal rats

Objective:To observe effect of granulocyte colony-stimulating factor(G-CSF) and restructure human thrombopoietin on hypoxic-ischemic brain damage(HIBD) in new born rats.Methods:A total of60 neonatalSD rats were selected and divided into4 groups, with15 in each group.Group A served as control group.Rats ofGroupsB-D were prepared forHIBD model by ligation of left common carotid artery combined with hypoxia method.Rats ofGroupA were only completed with free left common carotid artery without ligation and hypoxia operation.AfterHIBD model preparation,GroupB was administrated with subcutaneous injection of normal saline for placebo treatment;GroupC was administrated with cervical subcutaneous injection of0.5 μg/10 g granulocyte colony stimulating factor(G-CSF) for5 d(Once a day);GroupD was administrated with intraperitoneal injection of15U/10 g recombinant human thromobopoietin(rhTPO) for treatment.After modeling for7,14 and21 d,5 rats were sacrificed in each group, respectively. Brain quality damage(%) conditions of experimental animals in each group were compared in different time points, and cerebral histopathological changes of each group were observed. Expression of nestin in rats of each group was detected by immunohistochemical method. Results:After modeling for7,14 and21 d, brain quality damages(%) ofGroupsB,C andD were significant higher than that of inGroupA(P0.05). Conclusions:BothG-CSF andTPO can protect the nervous system ofHIBD neonatal rats. G-CSF can promote the proliferation and differentiation of neural precursor cells to decrease the degeneration and necrosis of nerve cell.TPO can obviously ameliorate morphology index ofHIBD rats.Through regulating ratio ofTIMP-1 andMMP-9,TPO can maintain the integrity of blood brain barrier to relieve the occurrence of brain damage.

Protective effect of granulocyte-colony-stimulating factor against chronic myocardial ischemia in rabbits / 西安交通大学学报(医学版)

Objective To investigate the protective effects and mechanisms of granulocyte-colony-stimulating factor (G-CSF)on a rabbit model of chronic myocardial ischemia.Methods Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits.Rabbits were subcutaneously injected with G-CSF (G-CSF group)or saline (control group)for 6 days after myocardial ischemia.The percentage of CD34-positive cells in the peripheral blood was evaluated by flow cytometry,and CD34-positive cells homing and vWF expression in the ischemic myocardium were determined by immunohistochemistry.Results Rabbits in G-CSF group had a higher survival rate than those in control group (P <0.05).Immunohistochemistry of the ischemic myocardium showed that compared with control group,G-CSF group had increased homing of CD34-positive cells on day 7 post-surgery,and more vessels on day 28 post-surgery by anti-von Willebrand factor staining.In addition,we observed an increase in the percentage of CD34-positive cells in the peripheral blood in G-CSF group.Conclusion G-CSF produces an obvious protective effect against chronic myocardial ischemia in rabbits by increasing stem cell mobilization,homing to ischemic myocardium and accelerating neovascularization.

Effect of G-CSF and TPO on HIBD in neonatal rats

OBJECTIVE@#To observe effect of granulocyte colony-stimulating factor (G-CSF) and restructure human thrombopoietin on hypoxic-ischemic brain damage (HIBD) in new born rats.@*METHODS@#A total of 60 neonatal SD rats were selected and divided into 4 groups, with 15 in each group. Group A served as control group. Rats of Groups B-D were prepared for HIBD model by ligation of left common carotid artery combined with hypoxia method. Rats of Group A were only completed with free left common carotid artery without ligation and hypoxia operation. After HIBD model preparation, Group B was administrated with subcutaneous injection of normal saline for placebo treatment; Group C was administrated with cervical subcutaneous injection of 0.5 μg/10 g granulocyte colony stimulating factor (G-CSF) for 5 d (Once a day); Group D was administrated with intraperitoneal injection of 15 U/10 g recombinant human thromobopoietin (rhTPO) for treatment. After modeling for 7, 14 and 21 d, 5 rats were sacrificed in each group, respectively. Brain quality damage (%) conditions of experimental animals in each group were compared in different time points, and cerebral histopathological changes of each group were observed. Expression of nestin in rats of each group was detected by immunohistochemical method.@*RESULTS@#After modeling for 7, 14 and 21 d, brain quality damages (%) of Groups B, C and D were significant higher than that of in Group A (P0.05).@*CONCLUSIONS@#Both G-CSF and TPO can protect the nervous system of HIBD neonatal rats. G-CSF can promote the proliferation and differentiation of neural precursor cells to decrease the degeneration and necrosis of nerve cell. TPO can obviously ameliorate morphology index of HIBD rats. Through regulating ratio of TIMP-1 and MMP-9, TPO can maintain the integrity of blood brain barrier to relieve the occurrence of brain damage.

Effect of G-CSF and TPO on HIBD in neonatal rats

Objective: To observe effect of granulocyte colony-stimulating factor (G-CSF) and restructure human thrombopoietin on hypoxic-ischemic brain damage (HIBD) in new born rats. Methods: A total of 60 neonatal SD rats were selected and divided into 4 groups, with 15 in each group. Group A served as control group. Rats of Groups B-D were prepared for HIBD model by ligation of left common carotid artery combined with hypoxia method. Rats of Group A were only completed with free left common carotid artery without ligation and hypoxia operation. After HIBD model preparation, Group B was administrated with subcutaneous injection of normal saline for placebo treatment; Group C was administrated with cervical subcutaneous injection of 0.5 μg/10 g granulocyte colony stimulating factor (G-CSF) for 5 d (Once a day); Group D was administrated with intraperitoneal injection of 15 U/10 g recombinant human thromobopoietin (rhTPO) for treatment. After modeling for 7, 14 and 21 d, 5 rats were sacrificed in each group, respectively. Brain quality damage (%) conditions of experimental animals in each group were compared in different time points, and cerebral histopathological changes of each group were observed. Expression of nestin in rats of each group was detected by immunohistochemical method. Results: After modeling for 7, 14 and 21 d, brain quality damages (%) of Groups B, C and D were significant higher than that of in Group A (. P0.05). Conclusions: Both G-CSF and TPO can protect the nervous system of HIBD neonatal rats. G-CSF can promote the proliferation and differentiation of neural precursor cells to decrease the degeneration and necrosis of nerve cell. TPO can obviously ameliorate morphology index of HIBD rats. Through regulating ratio of TIMP-1 and MMP-9, TPO can maintain the integrity of blood brain barrier to relieve the occurrence of brain damage.