Acute Alcoholic Hepatitis: New and Experimental Medications.

Outcomes of Pregnancies for Women with Severe Chronic Neutropenia with or without G-CSF Treatment.

Acute Kidney Injury in Alcohol-Associated Hepatitis: More than a Bystander

Nicotinamide (vitamin B3) treatment improves response to G‐CSF in severe congenital neutropenia patients

Granulocyte colony-stimulating factor and congenital neutropenia-risk of leukemia?

Massive inflammation and liver failure are main contributors to the high mortality in alcohol‐associated hepatitis (AH). In recent clinical trials, granulocyte colony‐stimulating factor (G‐CSF) therapy improved liver function and survival in patients with AH. However, the mechanisms of G‐CSF‐mediated beneficial effects in AH remain elusive. In this study, we evaluated effects of in vivo G‐CSF administration, using a mouse model of AH. G‐CSF treatment significantly reduced liver damage in alcohol‐fed mice even though it increased the numbers of liver‐infiltrating immune cells, including neutrophils and inflammatory monocytes. Moreover, G‐CSF promoted macrophage polarization toward an M2‐like phenotype and increased hepatocyte proliferation, which was indicated by an increased Ki67‐positive signal colocalized with hepatocyte nuclear factor 4 alpha (HNF‐4α) and cyclin D1 expression in hepatocytes. We found that G‐CSF increased G‐CSF receptor expression and resulted in reduced levels of phosphorylated β‐catenin in hepatocytes. In the presence of an additional pathogen‐associated molecule, lipopolysaccharide (LPS), which is significantly increased in the circulation and liver of patients with AH, the G‐CSF‐induced hepatoprotective effects were abolished in alcohol‐fed mice. We still observed increased Ki67‐positive signals in alcohol‐fed mice following G‐CSF treatment; however, Ki67 and HNF‐4α did not colocalize in LPS‐challenged mice. Conclusion: G‐CSF treatment increases immune cell populations, particularly neutrophil counts, and promotes M2‐like macrophage differentiation in the liver. More importantly, G‐CSF treatment reduces alcohol‐induced liver injury and promotes hepatocyte proliferation in alcohol‐fed mice. These data provide new insights into the understanding of mechanisms mediated by G‐CSF and its therapeutic effects in AH.

We investigated if bacteria type alters outcome with prophylactic granulocyte colony stimulating factor (G-CSF) therapy during pneumonia. Rats received G-CSF or placebo daily for 6 d and after the third dose were intrabronchially inoculated with either Escherichia coli or Staphylococcus aureus. Without G-CSF, E. coli and S. aureus produced similar (p = NS) mortality rates (36 versus 38%) and serial changes in mean circulating neutrophil counts (CNC), but differing mean (+/- SE) tumor necrosis factor (TNF) levels (E. coli, 259 +/- 104 versus S. aureus, 51 +/- 17 pg/ml, p = 0.01). G-CSF prior to bacteria increased mean CNC more than six times compared with placebo (p = 0.001). However, with G-CSF in the first 6 h after E. coli, there was a greater than 20-fold decrease in mean (+/- SE) CNC (x 10(3)/ mm3) to below placebo (0.5 +/- 0.1 versus 0.8 +/- 0.1), whereas with G-CSF after S. aureus, there was only a fivefold decrease in mean CNC and CNC were greater than placebo (1.8 +/- 0.2 versus 0.8 +/- 0.1) (E. coli versus S. aureus decrease in CNC with G-CSF, p = 0.001). With E. coli, G-CSF worsened oxygenation and increased bacteremia and mortality, whereas with S. aureus, G-CSF improved oxygenation and decreased bacteremia and mortality (G-CSF therapy, E. coli versus S. aureus, p = 0.03, 0.05, and 0.001, respectively). Thus, during S. aureus pneumonia with low TNF levels, G-CSF increased CNC and bacterial clearance, resulting in less pulmonary injury and decreased death. During E. coli pneumonia with high TNF levels, G-CSF paradoxically decreased CNC, resulting in impaired bacterial clearance and worsened pulmonary injury and death. Bacterial species and the associated inflammatory mediator response can alter outcome with prophylactic G-CSF therapy during pneumonia.

Efficacy of Granulocyte Colony-Stimulating Factor and N-Acetylcysteine Therapies in Patients With Severe Alcoholic Hepatitis

Study question Do intrauterine irrigations with peripheral blood mononuclear cell (PBMC) secretome, granulocyte-colony stimulating factor (G-CSF), stem cells improve reproductive outcomes in women with chronic endometritis (CE)? Summary answer Intrauterine administration of PBMC, G-CSF, SC, in addition to antibacterial therapy, significantly improved clinical pregnancy rates in women with CE What is known already Chronic endometritis (CE) is linked to recurrent implantation failure (RIF) and reduced pregnancy rates, even in women without infection symptoms. Antibiotic therapy remains the standard treatment but is often ineffective due to microbial resistance, biofilms, and undetected viral infections. Uterine factor infertility is less curable, as even euploid embryo transfer may not lead to pregnancy. Regenerative and immunomodulatory therapies offer alternatives: PBMCs modulate immunity, G-CSF promotes endometrial growth, and stem cells aid tissue regeneration. This study assesses the effects of intrauterine irrigations with these agents in CE patients with infertility. Study design, size, duration A prospective, randomized clinical trial included 110 women with long-term infertility (≥5 years) and multiple implantation failures. After screening, 54 patients with chronic endometritis were enrolled: the main group received standard antimicrobial therapy plus PBMCs, while the comparison group received standard therapy alone. Screening included medical history, informed consent, thrombophilia testing, and hysteroscopic microbial assessment. Additional studies evaluated G-CSF (n = 97), autologous bone stem cells (n = 60), and other regenerative approaches in recurrent implantation failure. Participants/materials, setting, methods rospective endometrial screening included bacterial and viral analysis (CMV, EBV, HPV, HSV 1,2,6,8). Endometrial IL and cytokine levels (TGFβ1, bFGF2, DEFa1) were analyzed in idiopathic infertility patients vs. fertile controls. Patients received intrauterine PBMC: Participants had long-term infertility, multiple implantation failures or recurrent pregnancy loss)and were screened for thrombophilia, autoimmune disorders, and microbial/viral infections. Endometrial samples were analyzed for microbiota composition and immune markers. Main results and the role of chance A significant decline in endometrial TGFβ1 and bFGF2 and an increase in DEFa1 were observed in CE patients compared to fertile women. 1. PBMC Therapy: Endometrial microbiota analysis showed a predominance of Lactobacillus spp. (81.3%) and Staphylococcus spp. (72.9%), with lower rates of Gardnerella and Candida. Viruses (CMV, HHV-6A, EBV, HSV-1) were detected in 6 patients, with no significant differences between groups. 6 patients conceived spontaneously, while 48 underwent FET. Clinical pregnancy rate (CPR) per transfer was 72% (18/25) in the PBMC group vs. 39.13% (9/23) in controls (p=0.022). Overall CPR was 76.66% (23/30) vs. 41.7% (10/24) (p=0.009). Cytokine profiling showed increased IL-18 and decreased IL-10/IL-18 ratio post-treatment, indicating improved immune modulation. 2. G-CSF Therapy: G-CSF significantly improved reproductive outcomes, with a higher CPR (69.7% vs. 45.5%, p=0.047) and live birth rate (63.64% vs. 39.39%, p=0.04). In Asherman’s syndrome, G-CSF therapy over 3–6 months significantly increased endometrial thickness (p<0.05), supporting its role in endometrial regeneration. 3. Stem Cell Therapy: MSC therapy resulted in a 23% СPR, with an average conception time of 9 months. Pregnancy rates were significantly higher (p<0.05), though endometrial thickness showed no significant increase (p>0.05). Limitations, reasons for caution The small sample size necessitates larger trials to confirm findings. Variability in CE diagnostic criteria and patient-specific endometrial conditions may affect reproducibility. Long-term safety and potential risks of intrauterine PBMC, G-CSF, stem cell administration require further investigation. Standardization of protocols for dosing and timing is essential Wider implications of the findings PBMC, G-CSF, SC, significantly improved implantation and pregnancy rates compared to standard therapy (p < 0.05). Future therapies may include fetal stem cells and VEGF-based interventions to enhance IVF success rates.Regenerative medicine offers a promising alternative to antibiotics for treating CE-related infertility, requiring further validation in larger trials. Trial registration number No

a front page story in The New York Times ([22][1]) at the end of March 2001 reported that “the basis of a possible revolution in treating heart attack patients has been laid by three reports of using stem cells from bone marrow to repair heart tissue in animals.” Those three reports ([11][2], [

Granulocyte colony-stimulating factor therapy for cardiac repair after acute myocardial infarction: A systematic review and meta-analysis of randomized controlled trials

Granulocyte colony stimulating factor (G-CSF) therapy has been reported to be proarrhythmic. The in vivo mobilization of endothelial progenitor cells (EPCs) and the possible proarrhythmic effects in patients with severe coronary artery disease (CAD) and inducible ischemia have not been described. We treated 8 patients (mean age = 69 +/- 10) suffering from severe CAD and angina pectoris (CCS 3 +/- 0.5) despite optimal medical therapy with subcutaneous G-CSF over 7 days to mobilize EPCs (CD34(+), CD117(+)). ECG monitoring was performed throughout the treatment period. A 24-hour ECG was recorded before and after G-CSF application. Mobilization of EPCs was monitored by fluorescent activated cell sorter (FACS-Calibur, Becton-Dickinson, Franklin Lakes, NJ, USA) analysis. Other medications remained unchanged. G-CSF therapy significantly increased peripheral leukocyte count from 7.45 +/- 2.4 to a peak of 42.2 +/- 10.9 x 10(3)/muL with a parallel rise in CD34(+) EPCs from 4.35 +/- 1.94 to 33.0 +/- 22.8/muL. The percentage of CD34(+)/CD117(+) cells changed from 0.32 +/- 0.25 to 0.24 +/- 0.28% (day of discharge, P = ns). During continuous ECG monitoring, no significant bradycardia, tachycardia, or changes in conduction were observed. Holter data collected after 7 days of G-CSF therapy showed no significant differences from baseline. A linear correlation (r = 0.76) was observed for the absolute values of deltaP wave duration and deltaCD34(+) concentration on day 2 compared to follow-up at 142 +/- 33 days, though it did not reach statistical significance (P = 0.29). This is the first study showing that mobilization of CD34(+) EPCs is safe in patients with severe CAD. The accompanying leukocytosis did not appear proarrhythmic. Changes in P wave duration might be attributable to G-CSF therapy.

Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection

Alcohol-associated hepatitis (AH) is the leading cause of liver-related mortality, with severe alcohol-associated hepatitis (SAH) showing a short-term mortality rate of 20%-50% even in developed countries. Corticosteroids are the only evidence-based pharmacologic treatment, but their efficacy is limited to short-term survival, with 30%-40% of patients achieving a complete response. Early liver transplantation (LT) has been explored as a salvage therapy for steroid-refractory SAH, but its feasibility is restricted by ethical concerns and donor shortages, particularly in Japan. In the absence of LT eligibility, patients are often left with the best supportive care, underscoring the urgent need for alternative salvage therapies. Recent studies have explored selective anti-inflammatory strategies targeting proinflammatory cytokines, such as TNFα and IL-1β. However, clinical trials have yet to demonstrate sufficient efficacy to outweigh the increased risk of infection. Granulocyte colony-stimulating factor (G-CSF) therapy has been investigated for its potential to promote liver regeneration, but its efficacy remains inconsistent across populations. Neutrophil-targeted therapies, including granulocyte-monocyte/macrophage apheresis (GMA), have emerged as a novel approach. Our recent pilot study demonstrated improved survival in patients with steroid-refractory SAH treated with GMA, supporting its potential as a safe and effective anti-inflammatory therapy. This review summarizes the latest advances in the treatment of SAH and emphasizes the need for novel salvage therapies to address unmet needs in steroid-refractory cases. Further research is essential to validate these new therapies and to optimize treatment strategies to improve the long-term prognosis of SAH.

Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial

The study aims to describe two promising therapeutic options for resistant "thin" endometrium in fertility treatment: granulocyte colony-stimulating factor (G-CSF) and stem cell therapy. A review of the scientific literature related to patients with thin endometrium undergoing fertility treatment. Sufficient endometrial growth is fundamental for embryo implantation. Whether idiopathic or resulting from an underlying pathology, a thin endometrium of <7mm is associated with lower probability of pregnancy; however, no specific thickness excludes the occurrence of pregnancy. We specifically reviewed two relatively new treatment options for resistant thin lining: intrauterine G-CSF and stem cell therapy. The majority of the reviewed trials showed a significant benefit for intrauterine G-CSF infusion in improving endometrial thickness and pregnancy rates. Early results of stem cell therapy trials seem promising. EMT <7mm is linked to lower probability of pregnancy in assisted reproductive technology. Intrauterine G-CSF infusion appears to be a potentially successful treatment option for resistant cases, while stem cell therapy seems to be a promising new treatment modality in severely refractory cases.