Effect Of Granulocyte Colony-stimulating Factor Research Articles

Large Vessel Vasculitis in a Patient Receiving G-CSF: A Possible Differential for Fever of Unknown Origin.

Large vessel vasculitis is a known but rare side effect of granulocyte colony-stimulating factor (G-CSF) therapy. We report a case of adenocarcinoma lung with pleural infiltration and mediastinal lymphadenopathy, who was treated with neoadjuvant chemotherapy and pegylated G-CSF. After three cycles, he developed a fever. He underwent F-18 fludeoxyglucose (FDG) positron emission tomography computed tomography for fever of unkwnown origin evaluation, which revealed a response to chemotherapy along with the appearance of FDG avid mural thickening in a few large arteries, suggesting a diagnosis of G-CSF-induced large vessel vasculitis.

The Effect of Granulocyte Colony-Stimulating Factor on Endometrial Receptivity of Implantation Failure Mouse.

The purpose of this study was to investigate the effect of G-CSF on the endometrial receptivity of implantation failure mice.Sixty female mice were treated mifepristone to establish an implant failure model. The treatment groups received different doses of G-CSF. Endometrial tissue and serum were collected on day 5 after mating. The abundance of pinopodes on the endometrium was observed by scanning electron microscopy. The expressions of LPAR3, COX2, and HOXA10 were detected by RT-qPCR and Western blotting. Serum levels of E2, P, VEGF, LIF, TNF-α and IL-10 were measured by ELISA. The expressions of VEGF, CD34, CD57, TNF-α, and IL-10 were assessed by immunohistochemistry. Immunofluorescence analysis was performed to determine the number of CD57, Treg, and Th17 cells.G-CSF increased implantation and pregnancy rates of mifepristone-induced implantation failure mice, with the most significant effect seen at the intermediate dose. G-CSF increased the serum levels of E2 and P, the abundance of endometrial pinopodes, and the level of LIF in the endometrium. It also promoted the expression of VEGF, HOXA10, LPAR3, and COX2. Moreover, G-CSF reduced the level of CD57 cells and the ratio of Th17/Treg cells in endometrium. G-CSF reduced the inflammatory factor TNF-α, but IL-10 did not change significantly.G-CSF can enhance embryo implantation rate and pregnancy rate and improve endometrial receptivity by attenuating degeneration of pinopodes, upregulating estrogen and progesterone, facilitating angiogenesis, maintaining immune cell homeostasis, and reducing the production of inflammatory cytokines in implantation failure mouse.

Role of Granulocyte Colony Stimulating Factor Effects on Unresponsive Thin Endometrium in Women Undergoing Controlled Ovarian Stimulated Intrauterine Insemination Cycles

Back Ground: It is a prospective observational study that included unexplained infertility cycles with COS –IUI protocols. Thin endometrium of less than 7mm has a negative effect on pregnancy rate. Endometrial function and receptivity factors are important in the success of implantation.
 Aim: To monitor the effects of G-CSF on thin endometrium in improving endometrium thickness and pregnancy rates in G-CSF administered COS-IUI cycles.
 Methods: This study was conducted in the Laxmi Narasimha hospital IVF center under the guidence Dr. Adaboina Anitha,Hanamkonda, warangal. Thin endometrium was defined less than 7mm on Trans vaginal ultrasound. Letrozole 5mg (2.5mg, BD) is used for ovulation induction on day 2 or day 3 of their cycle, G CSF 300units was added with significantly improved pregnancy rates in ART cycles. Trigger used was injection 10,000IU urinary hCG & 300 units G-CSF was instilled into the uterus. After 48hours ET was measured & IUI was performed under aseptic precautions. After 16 days β -hCG levels were monitored to determine whether there is a pregnancy.
 Results: In present study, we concluded that, 250 COS-IUI cycles were analysed and 50 cycles showed a thin endometrium and in them G-CSF was used. The pregnancy rate (28%) was evaluated, 14 members are positive for pregnancy.
 Conclusion: In our study we concluded that G-CSF and letrozole will improve increases endometrium thickness and conceiving rates in COS-IUI cycles.

Role of granulocyte colony stimulating factor (G-CSF) in dengue patients with severe thrombocytopenia.

To determine the effects of granulocyte colony-stimulating factor in improving platelet count in patients with dengue fever. The retrospective, cross-sectional study was conducted at Northwest General Hospital and Research Centre, Peshawar, Pakistan, between January 2021 and October 2022, and comprised dengue fever inpatients regardless of age and gender who received granulocyte colony-stimulating factor subcutaneously. The impact of colony-stimulating factor on platelet and white blood cell counts as well as any unfavourable consequences was assessed. Convenient sampling was used and a structured format was used for data collection. Data was analysed using SPSS 21. Of the 100 patients, 67(67%) were males and 33(33%) were females. The largest age group was that of >55 years 31(31%), fever was present in all the 100(100%) cases, bleeding in 18(18%) and platelet count <30,000 in 83(83%) cases. Dengue fever was confirmed by rapid dengue nonstructural protein 1 antigen in 76(76%) cases, dengue immunoglobulin G antibody test 28(28%), and immunoglobulin M antibody test in 31(31%) cases. Overall, 72(72%) patients received only one dose of granulocyte colony-stimulating factor. Post-administration, a substantial rise in the median platelet and white blood cell counts was seen compared to the baseline (p<0.05) on day 2. Granulocyte colony-stimulating factor helped increase platelet and white blood cell counts quickly in dengue fever patients.

Granulocyte colony-stimulating factor induces the migration of non-resident cells to intracerebral hemorrhage

The aim of the study is to determine the effect of granulocyte colony-stimulating factor (rHuG-CSF) on the migration of non-resident cells into the region of intracerebral hemorrhage (ICH), which can potentially be considered as mesenchymal stem cells. Materials and methods. In the experiment, unilateral ICH was simulated in rats by injection of autologous blood into the right hemisphere. Immunohistochemical method was used to study perihematomal area on day 1, 3, 10, 30, and 60 after ICH modeling. The appearance of cells expressing CD44, CD68, and CD146 markers was evaluated on a 3-point scale after penetrating trauma (PT) of the brain, ICH, and ICH with the growth factor injection (ICH/rHuG-CSF). Results. In contrast to PT, ICH intensified the infiltration of CD44+ cells in the perihematomal area of the brain and caused the appearance of CD68+ and CD146+ cells in hemorrhage. The specific density of CD44+ cells was decreased on day 60 after ICH, and the effect of rHuG-CSF consisted in reducing the density of CD44+ cells on days 30 and 60. The appearance of CD68+ and CD146+ cells in the perihematomal area was seen after 10 days and further their detection was rare, while after the rHuG-CSF injection, the infiltration by cells with a similar immunophenotype was detected on day 3 ICH with a tendency to accumulate. Conclusions. Infiltration by cells expressing CD44, CD68, and CD146 into the perihematomal area of the rat brain was heterogeneous as to the time after brain injury. The appearance of cells with specified immunophenotype could be associated with hematoma elimination, angiogenesis processes, and other mechanisms of the perihematomal brain region remodeling, in which mesenchymal stem cells were involved. rHuG-CSF modulated the migration of CD68+ and CD146+ cells, which consisted in their earlier and more intense migration to the damaged area of the brain after ICH.

The Effect of Granulocyte Colony-Stimulating Factor (G-CSF) on Early Complications and Graft-Versus-Host Disease (GVHD) in Allogeneic Stem Cell Transplantation (ASCT) Recipients.

Objectives Granulocyte colony-stimulating factor (G-CSF) is commonly used to accelerate neutrophil recovery after allogeneic stem cell transplantation (ASCT) in most transplant centers. There was no consensus on the optimal use of G-CSF after ASCT. Although we useG-CSF to minimize morbidity and mortality, G-CSF can increase the risk of graft-versus-host disease (GVHD). In our study, we want to show the effect of prophylactic G-CSF on infection frequency, neutrophil and platelet engraftment, the duration of neutropenia, the development of GVHD, hospitalization time, and transplant-related mortality (TRM) after ASCT. Materials and methods One hundred (71 males and 29 females) patients who did not receive G-CSF and 100 (58 males and 42 females) patients who received prophylactic G-CSF were included in the study. Results Age, diagnosis, the time between diagnosis and transplantation, preparation regimen, donor type, and the number of infused cluster of differentiation (CD) 34+ cells were not different in both groups (p>0.05). The frequency of female patients was higher in the group receiving G-CSF. Febrile neutropeniawas more frequent in patients who did not receive G-CSF. Neutrophil engraftment and platelet engraftment were detected longer in patients not receiving G-CSF. The frequency of veno-occlusive disease (VOD) and hyperacute, chronic, andacute GVHD was not different in both groups (p>0.05). One hundred-day TRMand five-year overall survival (OS) were similar in the two groups (p>0.05). Conclusions Our study supports that G-CSF usage does not cause an increase in the frequency of GVHD and has a positive effect on the process by accelerating myeloid engraftment. In light of the data in our study, we can say that the use of G-CSF should be investigated in a randomized controlled clinical trial.

Effect of Granulocyte Colony-Stimulating Factor on the Development of Spermatogenesis in the Adulthood of Juvenile AML Mice Model Treated with Cytarabine.

Pediatric acute myeloid leukemia (AML) generally occurs de novo. The treatment of AML includes cytarabine (CYT) and other medications. The granulocyte-colony stimulating factor (GCSF) is used in the clinic in cases of neutropenia after chemotherapies. We show that the administration of GCSF in combination with CYT in AML-diagnosed mice (AML+CYT+GCSF) extended the survival of mice for additional 20 days. However, including GCSF in all treatment modalities does not affect the testis' weight or the histology of the seminiferous tubules (STs). We show that GCSF does not affect normal ST histology from AML-, CYT-, or (AML+CYT)-treated groups compared to the relevant treated group without GCSF 2, 4, and 5 weeks post-injection. However, when comparing the percentages of normal STs between the AML+CYT+GCSF-treated groups and those without GCSF, we observe an increase of 17%-42% in STs at 4 weeks and 5.5 weeks post-injection. Additionally, we show that the injection of GCSF into the normal, AML-alone, or CYT-alone groups, or in combination with AML, significantly decreases the percentage of STs with apoptotic cells compared to the relevant groups without GCSF and to the CT (untreated mice) only 2 weeks post-injection. We also show that injection of GCSF into the CT group increases the examined spermatogonial marker PLZF within 2 weeks post-injection. However, GCSF does not affect the count of meiotic cells (CREM) but decreases the post-meiotic cells (ACROSIN) within 4 weeks post-injection. Furthermore, GCSF not only extends the survival of the AML+CYT-treated group, but it also leads to the generation of sperm (1.2 ± 0.04 × 106/mL) at 5.5 weeks post-injection. In addition, we demonstrate that the injection of GCSF into the CT group increases the RNA expression level of IL-10 but not IL-6 compared to CT 2 weeks post-treatment. However, the injection of GCSF into the AML-treated group reverses the expression levels of both IL-10 and IL-6 to normal levels compared to CT 2 weeks post-injection. Thus, we suggest that the addition of GCSF to the regimen of AML after CYT may assist in the development of future therapeutic strategies to preserve male fertility in AML prepubertal patients.

Hypercoagulability in Pediatric Autologous Hematopoietic Progenitor Cell Collection – Is it the Time to Reconsider Screening? – A Case Report

Peripheral blood hematopoietic progenitor cell harvest by apheresis in pediatric patients, a double-edged sword, has advantages and disadvantages over conventional bone marrow transplantation. The effect of granulocyte colony-stimulating factor (G-CSF) mobilization on hemostasis in literature is very scarce. A 3-year-old female child with metastatic neuroblastoma planned for autologous transplant. Following G-CSF mobilization (75 mg; 4 days), the procedure was performed with all default parameters in Spectra Optia with an acid citrate dextrose (ACD) flow rate 1:12, assuming 3-total blood volume (TBV) to be processed with 150 ml of expected collection with target yield of 6 × 106 CD34 cells/kg. Despite normal coagulation laboratory parameters, it was abandoned for reasons such as low-flow alarms and thrombi in the kit tubings. In the subsequent procedures, the ACD to whole blood ratio was decreased to 1:16, and used bolus of heparin was followed by continuous heparin infusion throughout the procedure. Despite using heparin anticoagulation, a long thrombus was aspirated at needleless port. The procedure was completed with continuous low-flow alarms. A cumulative dose of 5.67 × 106 CD34 cells/kg was achieved over four procedures, but the cause of hypercoagulability was unknown. All the coagulation parameters were within normal limits before and after the procedure. The exact cause for hypercoagulability remains elusive. There are no studies or case reports in the pediatric population on hypercoagulability following apheresis procedure after G-CSF mobilization, but evidence is available for adults, with lack of explanation. It can also be due to low draw flow from the patient side or embolization of thrombi developed in the anticoagulant unprimed site in the kit tubings. More extensive studies are required to explain the mechanism of hypercoagulability during apheresis procedures in the pediatric population.

Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis.

Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury. To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI. We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria. Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy. Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.

Application of G-CSF in high-leukocyte acute myeloid leukemia is a poor prognostic factor

ABSTRACTObjectiveTo analyze the effect of granulocyte colony-stimulating factor (G-CSF) on outcomes in patients with acute myeloid leukemia (AML).MethodsA total of 526 patients with AML in the Haematology Department were enrolled. They were divided into a G-CSF treatment group and a no G-CSF group according to whether G-CSF was administered in the induction chemotherapy period, with 355 cases in the G-CSF group and 171 cases in the no G-CSF group. Cox regression analysis and Kaplan-Meier curve analysis were used to analyze the effect of G-CSF on the first complete remission (CR1) phase and overall survival (OS). In addition, further analysis was performed based on an initial white blood cell count of 50 * 10^9/L.ResultsThe application of G-CSF significantly shortened the CR1 phase and OS in patients with high leukocytes.ConclusionsG/GM-CSF should be used with caution in patients with AML, especially those with high leukocytes.

Immunomodulatory effect of granulocyte colony-stimulating factor in repeated implantation failures in embryo transfer programs

The objective: to determine the effectiveness of intrauterine administration of granulocyte colony-stimulating factor depending on endometrium immune phenotype in patients with repeated implantation failures in embryo transfer programs.Material and methods. Endometrial biopsy during the implantation window in an artificial cycle before and (in some patients) after intrauterine administration of granulocyte colony-stimulating factor (G-CSF) was performed in 42 patients with repeated implantation failures and gestational carriers (20 women) as a control group. Flow cytometry was used to count classes and subclasses of endometrial lymphocytes in endometrial tissue samples.Results. The population of endometrial immune cells in patients with repeated implantation failures and fertile women was compared. Pregnancy and live birth rates depending on endometrium immune phenotype in patients with repeated implantation failures after intrauterine administration of granulocyte colony-stimulating factor in embryo transfer program were determined and the effect of intrauterine administration of granulocyte colony-stimulating factor on endometrial immune phenotype was evaluated.High expression of HLA-DR and CD16 on uterine natural killers is reliably associated with successful implantation after intrauterine administration of granulocyte colony-stimulating factor in an embryo transfer program. It was established that in the group with an immature immune endometrial phenotype the frequency of pregnancy (53.8 %) and the frequency of live births (53.8 %) were twice higher compared to the rest of the patients with other variants or the absence of changes in the immune profile (pregnancy rate and frequency live birth rate – 26.9 %).Conclusions. One-third of patients with repeated implantation failures in genetically tested embryos transfer programs have a unique immune status of endometrium characterized by high expression of HLA-DR and CD16 on uterine natural killers. Intrauterine administration of granulocyte colony-stimulating factor leads to decrease of HLA-DR and CD16 expression on uterine natural killers and promotes successful implantation in embryo transfer program in this group of patients.

The effect of granulocyte-colony stimulating factor, decitabine, and busulfan–cyclophosphamide versus busulfan–cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial

Relapse remains high in patients with myelodysplastic syndrome-refractory anaemia with excess blasts (RAEB) or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate whether granulocyte-colony stimulating factor (G-CSF) and decitabine plus busulfan-cyclophosphamide conditioning reduced relapse compared with busulfan-cyclophosphamide in this population. We did an open-label, randomised, phase 3 trial at six hospitals in China. Eligible patients (aged 14-65 years) had myelodysplastic syndrome-RAEB or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome, and an Eastern Cooperative Oncology Group performance status of 0-2 and HSCT comorbidity index of 0-2. Patients were randomly assigned (1:1) to receive G-CSF, decitabine, and busulfan-cyclophosphamide conditioning or busulfan-cyclophosphamide conditioning. Randomisation was done with permuted blocks (block size four) with no stratification and was implemented through an interactive web-based response system, which was independent of study site staff and investigators. G-CSF, decitabine, and busulfan-cyclophosphamide conditioning comprised G-CSF 5 μg/kg daily subcutaneously (days -17 to -10), decitabine 20 mg/m2 daily intravenously (days -14 to -10), busulfan 3·2 mg/kg daily intravenously (days -7 to -4), and cyclophosphamide 60 mg/kg daily intravenously (days -3 and -2). Busulfan-cyclophosphamide conditioning comprised the same dose and duration of busulfan and cyclophosphamide. The primary endpoint was 2 year cumulative incidence of relapse. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02744742; the trial is complete. Between April 18, 2016, and Sept 30, 2019, 297 patients were screened for eligibility, 202 of whom were randomly assigned to G-CSF, decitabine, and busulfan-cyclophosphamide (n=101) or busulfan-cyclophosphamide (n=101) conditioning. 123 (61%) participants were male and 79 (31%) were female. Median follow-up was 32·4 months (IQR 10·0-43·0). The 2-year cumulative incidence of relapse was 10·9% (95% CI 5·8-17·9) in the G-CSF, decitabine, and busulfan-cyclophosphamide group and 24·8% (16·8-33·5) in the busulfan-cyclophosphamide group (hazard ratio 0·39 [95% CI 0·19-0·79]; p=0·011). Within 100 days after transplantation, the most common grade 3-4 adverse events in the G-CSF, decitabine, and busulfan-cyclophosphamide group and the busulfan-cyclophosphamide group were infections (34 [34%] and 32 [32%]), acute graft-versus-host disease (30 [30%] and 30 [30%]), and gastrointestinal toxicity (28 [28%] and 29 [29%]). 11 (11%) patients in the G-CSF, decitabine, and busulfan-cyclophosphamide group and 13 (13%) in the busulfan-cyclophosphamide group died of adverse events. There were no treatment related deaths. Our results suggest that G-CSF, decitabine, and busulfan-cyclophosphamide conditioning is a better choice than busulfan-cyclophosphamide conditioning for patients with myelodysplastic syndrome-RAEB or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic HSCT. This conditioning could be a suitable therapuetic option for this patient population. None. For the Chinese translation of the abstract see Supplementary Materials section.

The Effectiveness of Granulocyte Colony-Stimulating Factor (G-CSF) Against Experimental Ischemia-Reperfusion Injury in Rat Ovaries and Its Effect on In Vitro Fertilization Outcomes.

Local ischemic damage resulting from ovarian torsion is a common cause of decreased follicular activity and infertility. It was aimed to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) protection on in vitro fertilization (IVF) results against experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries. The study consisted of 35 adult female Sprague-Dawley albino rats (sham, ischemia, I/R, I + G-CSF, and I/R + G-CSF) randomly assigned to 5 groups, each containing 7 rats. While bilateral adnexal torsion was applied to the ischemia groups for 3h, detorsion was applied to the reperfusion groups. Intraperitoneal 100IU/kg G-CSF was administered 30min prior to ischemia (I + G-CSF) or reperfusion (I/R + G-CSF). After ovulation induction (intraperitoneal 150-300IU/kg PMSG), the oocytes were collected and IVF was applied. Statistically significant differences were observed between the collected oocyte numbers in I and I + G-CSF, I/R, and I/R + G-CSF groups (P values were P = 0.001 for the I-I + G-SCF groups and P = 0.003 for I/R-IR + G-CSF, respectively). An increase in the number of MII oocytes obtained was observed in the I + G-CSF and I/R + G-CSF groups compared to the I and I/R groups. Grade 1 and grade 2 embryo numbers were statically different between the I/R and I/R + G-CSF groups (P values were P = 0.023 for grade 1 embryos and P = 0.045 for grade 2 embryos, respectively). G-CSF treatment was found to be effective in reducing I- and I/R-induced ovarian damage.

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma

Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11–4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T.

Effect of Granulocyte Colony-Stimulating Factor (G-CSF) on Improving Impairment Scale After Acute Spinal Cord Injury: An Individual Participant Data Meta-Analysis

Background and Aim: The present study was conducted to investigate the effects of granulocyte colony-stimulating factor (G-CSF) after acute spinal cord injury on increasing a grade of improvement entitled American spinal cord injury association impairment scale (AIS) as an individual participant data (IPD) meta-regression analysis of clinical trials. Methods and Materials/Patients: According to our search strategy, four studies were selected. Multilevel ordered logistic regression modeling was used to predict AIS grade with G-CSF administration and time variable (first day and a 3-month follow-up). The IDs of the studies as well as the time series variable were imported to the random part of the model. Odds ratio (OR) and 95% confidence interval (CI) were reported. Results: A total of 277 samples were studied. A fixed effect model was performed at first. Accordingly, using G-CSF was associated with increased AIS grade (lower impairment) (OR=1.503, 95% CI=1.110-2.035) adjusted with time series (OR=1.868, 95% CI=1.378-2.532). In the mixed effect model, G-CSF was again associated with increased AIS grade (OR=1.780, 95% CI=1.301- 2.436) adjusted with time series (OR=2.152, 95% CI=1.406-3.294). Conclusion: The present meta-analysis showed the protective effect of GCS-F observed as an improvement in AIS grade. This protecting effect was further after adjusting the random effects of time series and individual studies. Although multilevel modeling could reduce our limitations, it should be regarded that the number of trials was not enough to establish strong conclusions.

Liver regeneration as treatment target for severe alcoholic hepatitis.

Severe alcoholic hepatitis (AH) is a distinct entity in the spectrum of alcohol-related liver disease, with limited treatment options and high mortality. Supportive medical care with corticosteroids in selected patients is the only currently available treatment option, often with poor outcomes. Based on the insights into the pathogenetic mechanisms of AH, which are mostly obtained from animal studies, several new treatment options are being explored. Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target. Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor (G-CSF) on liver regeneration and immunomodulation in animal models, several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH. Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH, these effects were not confirmed by a recently published multicenter randomized trial, suggesting that other options should rather be pursued. Stem cell transplantation represents another option for improving liver regeneration, but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing, with established lack of efficacy in patients with compensated cirrhosis. In this review, we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration. The lack of high-quality studies and evidence is a major obstacle in further treatment development. New insights into the pathogenesis of not only liver injury, but also liver regeneration processes are mandatory for the development of new treatment options. A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing, and data obtained from animal studies are essential for future research.

Granulocyte colony stimulating factor (GCSF) did not affect the fertility outcomes in women with unexplained infertility after intrauterine insemination: a randomised clinical trial

This study aimed to evaluate the effect of granulocyte colony stimulating factor (GCSF) on fertility outcomes in women with unexplained infertility after intrauterine insemination (IUI). This study is a randomised clinical trial that was conducted on unexplained infertile women referred to infertility Clinic in Yasuj, Iran. All participants were stimulated by letrozole, clomiphene and HMG during the cycle. When at least one follicle was greater than 18 mm, 5000 IU hCG intramuscularly was administered for ovulation induction and then IUI was performed 34–36 hours later. In GCSF group, 300 μg GCSF subcutaneously administrated in two days after IUI. Control group received routine IUI. The main outcome measures were biochemical pregnancy, clinical pregnancy, abortion and ongoing pregnancy rate. Our results showed no statistically significant difference in the biochemical pregnancy (16.3% vs. 12.2%; P=.56), clinical pregnancy (16.3% vs. 8.2%; P=.21), abortion (0 vs. 2.04%; P=.55) and ongoing pregnancy rates (8.2% vs. 14.2%; P=.32) between the control and the G-CSF groups. The results of the current study suggest that systemic administration of 300 μg GCSF in the two days after receiving IUI in patients with unexplained infertility does not offer any beneficial clinical related implantation, and pregnancy rates. IRCT registration number: IRCT20160524028038N4 Impact statement What is already known on this subject? Unexplained infertility means to the inability of couples in pregnancy after a year without obvious male and female infertility factors. Some patients have not been justified in endometrial function, which leads to the defect of the dialogue between the foetus and endometrium and may lead to implantation failure. Granulocyte colony stimulating factor is produced at the maternal-foetal interface during embryo implantation and is the main part of the uterine-cytokine network that is needed to create and maintain pregnancy. What do the results of this study add? The current study suggests that systemic administration of 300 μg granulocyte colony stimulating factor in the two days after receiving IUI in patients with unexplained infertility does not offer any beneficial clinical related implantation and pregnancy rates. What are the implications of these findings for clinical practice and/or further research? These results may not be generalised to all patients and more randomised controlled trials are needed for the comparison of granulocyte colony stimulating factor effects on women with thin and normal endometrial thickness, efficacy, side effects, and pregnancy outcomes of the intrauterine perfusion versus systemic subcutaneous administration of granulocyte colony stimulating factor in unexplained infertility treated with intrauterine insemination.

Granulocyte colony-stimulating factor with or without immunosuppression reduction in neutropenic kidney transplant recipients.

Neutropenia post-kidney transplantation is associated with adverse graft and patient outcomes. We aimed to analyze the effect of granulocyte colony-stimulating factor (G-CSF) use with and without immunosuppression reduction on graft outcomes in neutropenic recipients. In this retrospective cohort study, we identified 120 recipients with neutropenia, within the first-year post-transplant. Of these, 45.0% underwent no intervention, 17.5% had immunosuppression reduced, 18.3% were only given G-CSF, and 19.2% had both interventions. Overall, 61 patients experienced the composite outcome of de-novo DSA, biopsy-proven acute rejection, and all-cause graft failure and the cumulative incidence of this outcome did not vary by any of the four interventions (p=.93). When stratifying the cohort by G-CSF use alone, those who received G-CSF were more likely to have had severe neutropenia (<500/mm3 : 51.1% vs. 12.0%, p<.001), and immunosuppression reduction (51.1%vs. 28.0%, p=.003). However, the composite outcome was not different in the G-CSF and no G-CSF cohort (53.3%vs. 49.3%, p=.67), and in a multivariate model, G-CSF use was not associated with this outcome (aHR=1.18, 95% CI: .61-2.30). However, a trend towards higher DSA production was noted in the G-CSF cohort (87.5%vs. 62.2%) and this observation warrants prospective evaluation. Overall, we conclude that G-CSF use with or without immunosuppression reduction was not associated with graft outcomes.

The effects of granulocyte-colony stimulating factor on chronic liver disease: a meta-analysis.

The clinical application of granulocyte-colony stimulating factor on chronic liver disease is still controversial. The study aimed to evaluate the effects of granulocyte-colony stimulating factor on chronic liver disease. A systematic literature search was performed in PubMed, Embase, Cochrane Library and Chinese Biomedical Literature database. Randomized-controlled trials assessing the efficacy of granulocyte-colony stimulating factor were selected. Granulocyte-colony stimulating factor was associated with an increasing long-term survival (RR 1.54; 95% CI 1.22 to 1.94; p = 0.0003; heterogeneity: Q = 0.26, I2 = 25%) and an increasing short-term survival (RR 1.44; 95% CI 1.16 to 1.78; p = 0.0009; heterogeneity: Q < 0.00001, I2 = 80%). Granulocyte-colony stimulating factor failed to lower mortality secondary to multiple organ failure (RR 0.65; 95% CI 0.34 to 1.21; p = 0.17; heterogeneity: Q = 0.45; I2 = 0%), gastrointestinal bleeding mortality (RR 0.97; 95% CI 0.61 to 1.56; p = 0.91; heterogeneity: Q = 0.35; I2 = 11%) and sepsis mortality (RR 0.27; 95% CI 0.06 to 1.12; p = 0.07; heterogeneity: Q < 0.00001; I2 = 90%). It significantly lowered the Child-Turcotte-Pugh (MD=-0.97, 95% CI -1.48 to -0.45; p = 0.0003; heterogeneity: Q = 0.25; I2 = 28%). No serious adverse events were observed. Granulocyte-colony stimulating factor resulted in significantly improved 12-month survival and reduced Child-Turcotte-Pugh score with relative safety. Establishment of guidelines and protocols in future clinical trials will promote granulocyte-colony stimulating factor as an effective and safe therapy for chronic liver disease.

Investigation of the effectiveness of granulocyte colony-stimulating factor (G-CSF) in the treatment of atrophic rhinitis

Investigation of the effectiveness of granulocyte colony-stimulating factor (G-CSF) in the treatment of atrophic rhinitis