Trends in the use of granulocyte colony stimulating factors for older patients with cancer, 2010 to 2019.

INTRODUCTION: Older patients with cancer receiving myelosuppressive treatment are at an increased risk for developing febrile neutropenia (FN) or having chemotherapy dose-reductions or delays, resulting in suboptimal health outcomes. Granulocyte colony stimulating factors (G-CSF) are effective medications to reduce these adverse events and are recommended for patients ≥65 years receiving chemotherapy with >10 % FN risk. We sought to characterize the trends and predictors of G-CSF use between the youngest-old (66-74 years), middle-old (75-84 years), and oldest-old (≥85 years) patients with cancer. MATERIALS AND METHODS: We used registry data from SEER-Medicare for breast, lung, ovarian, colorectal, esophageal, gastric, uterine, prostate, pancreatic cancer, and non-Hodgkin lymphoma (NHL) diagnoses from 2010 to 2019. Cox proportional hazard analysis was used. RESULTS: Overall, 41.4 % of patients received G-CSF from chemotherapy initiation to three days after completion of the first chemotherapy course. The use rate remained relatively stable for all cancers, except for an increase in use for those with pancreatic cancer. G-CSF use decreased as patients got older. The oldest-old were 43.0 % (95 % confidence interval: 40.7-45.2 %) less likely to receive G-CSF compared to the youngest-old. Patients with breast cancer or NHL were more likely to receive G-CSF than those with other cancers. Patients who were female, married, White or Hispanic, and had fewer comorbidities were more likely to receive G-CSF. DISCUSSION: G-CSF is used less often in populations at higher risk of developing FN and related complications. Improving adherence to recommendations can improve health outcomes, especially in the oldest adults, older males, and Black patients.

Drug-induced pneumonitis risk in diffuse large B-cell/follicular lymphoma patients treated with R-CHOP-like regimen is associated with the use of granulocyte colony-stimulating growth factors.

BACKGROUND: Rituximab-based combinations are the standard of care in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug-induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony-stimulating factors (G-CSF) are supportive agents commonly used to prevent neutropenic infections. G-CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. METHODS: In this retrospective study, we reported the G-CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R-CHOP-type immunochemotherapy. RESULTS: In 72% of patients, the treatment included a G-CSF support. The overall incidence of treatment-induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G-CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3-4) also increased the risk of DIP. CONCLUSIONS: These findings suggest that the use of G-CSF increases the risk of DIP, when used in combination with rituximab-containing regimen.

Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

The PPARα agonist fenofibrate reduces the cytokine imbalance in a maternal immune activation model of schizophrenia.

Maternal infections during pregnancy may increase the risk of psychiatric disorders in offspring. We recently demonstrated that activation of peroxisome proliferator-activate receptor-α (PPARα), with the clinically available agonist fenofibrate (FEN), attenuates the neurodevelopmental disturbances induced by maternal immune activation (MIA) in rat offspring. We hypothesized that fenofibrate might reduce MIA-induced cytokine imbalance using a MIA model based on the viral mimetic polyriboinosinic-polyribocytidilic acid [poly (I:C)]. By using the Bio-Plex Multiplex-Immunoassay-System, we measured cytokine/chemokine/growth factor levels in maternal serum and in the fetal brain of rats treated with fenofibrate, at 6 and 24 h after poly (I:C). We found that MIA induced time-dependent changes in the levels of several cytokines/chemokines/colony-stimulating factors (CSFs). Specifically, the maternal serum of the poly (I:C)/control (CTRL) group showed increased levels of (i) proinflammatory chemokine macrophage inflammatory protein 1-alpha (MIP-1α), (ii) tumor necrosis factor-alpha (TNF-α), the monocyte chemoattractant protein-1 (MCP-1), the macrophage (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, in the fetal brain of the poly (I:C)/CTRL group, interleukin 12p70 and MIP-1α levels were lower than in vehicle (veh)/CTRL group. Notably, MIP-1α, TNF-α, keratinocyte derived chemokine (GRO/KC), GM-CSF, and M-CSF levels were lower in the poly (I:C)/FEN than in poly (I:C)/CTRL rats, suggesting the protective role of the PPARα agonist. PPARα might represent a therapeutic target to attenuate MIA-induced inflammation.

Impact of treatment experience on patient knowledge of colony-stimulating factors among patients receiving cancer chemotherapy: evidence from S1415CD-a large pragmatic trial.

PURPOSE: Primary prophylactic granulocyte colony-stimulating factors (PP-CSFs) are prescribed alongside chemotherapy regimens that carry a significant risk of febrile neutropenia (FN). As part of S1415CD, a prospective, pragmatic trial evaluating the impact of automated orders to improve PP-CSF prescribing, we evaluated patients' baseline knowledge of PP-CSF and whether that knowledge improved following the first cycle of chemotherapy. METHODS: Adult patients with breast, colorectal, or non-small-cell lung cancer initiating chemotherapy were enrolled in S1415CD between January 2016 and April 2020. Eight questions assessing knowledge of CSF indications, risks, benefits, and out-of-pocket costs were included in a baseline survey and in a follow-up survey at the end of the first cycle of chemotherapy. Responses were stratified by the trial arm and whether chemotherapy was low, intermediate, or high FN risk. RESULTS: Of the 3605 eligible patients, 3580 (99.3%) completed the baseline survey, and 3420 (95.5%) completed the follow-up survey. At baseline, 803 (22.4%) patients responded "Don't know" to all 8 questions, and all patients averaged 2.75 correct questions. At follow-up, knowledge increased by 0.34 in the high-FN-risk group (p < 0.001) but declined for the other FN-risk groups. In multivariate analysis, receiving a high-FN-risk regimen and younger age were significantly associated with knowledge improvement. CONCLUSION: Chemotherapy patients had poor knowledge of PP-CSF that improved only modestly among recipients of high-FN-risk chemotherapy. Further efforts to inform patients about the risks, benefits, and costs of PP-CSF may be warranted, particularly for those in whom prophylaxis is indicated. TRIAL REGISTRATION: NCT02728596, April 6, 2016.

Incidence and risk factors for febrile neutropenia of patients with diffuse large B-cell lymphoma receiving R-CHOP-21 in China.

OBJECTIVE: Febrile neutropenia (FN) is a serious complication of patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP-21. The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSFs for patients receiving chemotherapy with FN risk of 20% or 10 to 20% with defined risk factors. However, there are few studies on the incidence and risk factors of FN in patients with DLBCL receiving R-CHOP-21, especially in patients without primary G-CSF prophylaxis. METHODS: We conducted a retrospective analysis for the clinical data of 103 patients with DLBCL who underwent first R-CHOP-21 without primary G-CSF prophylaxis. The objective of the assessment was the incidence and risk factors of FN after the first chemotherapy cycle. RESULTS: After the first chemotherapy cycle, the incidence of FN was 20.4%. Multivariate analysis showed that age ≥ 65 years, bone marrow involvement, albumin < 35 g/L, and average relative dose intensity ≥ 80% were independent risk factors for FN. According to risk factors, we created a risk score system. The incidence of FN in the low-, intermediate- and high-risk groups was 5.6%, 17.2%, and 61.9%, respectively. CONCLUSION: Our data indicated that R-CHOP-21 itself is associated with a high-risk regiment for FN. We recommend that intermediate/high-risk patients should actively consider primary G-CSF prophylaxis to reduce the incidence of FN after chemotherapy.

A multinational, drug utilization study of lipegfilgrastim use in real-world setting in Europe.

PURPOSE: Lipegfilgrastim (Lonquex, Teva Pharma B.V.) is approved for reduction in neutropenia duration and febrile neutropenia incidence. In the framework of lipegfilgrastim regulatory approval in the EU, the Health Authorities requested a drug utilization study. This study was conducted to characterize prescribing patterns of lipegfilgrastim and quantify the extent of on- and off-label use of lipegfilgrastim in real-world setting in Europe. METHODS: Information on lipegfilgrastim use between January 2014 and March 2020 was abstracted from medical records in hospital and outpatient clinical settings. Indication for lipegfilgrastim was classified either as on-label or off-label use according to pre-determined criteria. The primary endpoint was the extent of lipegfilgrastim off-label use based on the most recent lipegfilgrastim cycle. RESULTS: Records of 481 patients were obtained from five European countries. Lipegfilgrastim was most commonly prescribed for prevention of neutropenia by oncologists and hematologists. Patients who were administered lipegfilgrastim were primarily ≥ 55 years old (65.1%) and female (65.7%). The most frequent underlying diagnosis was breast cancer (38.3%). For the most recent lipegfilgrastim cycle, on-label use was recorded in 452/459 patients with no missing data (98.5%), while off-label use was recorded in 7/459 patients (1.5%). The majority of off-label use was attributed to use with non-cytotoxic chemotherapy (57.1%). Off-label use of lipegfilgrastim across all treatment cycles with no missing data was 11/1547 cycles (0.7%). CONCLUSION: Using real-world data, these findings confirm the low rate of lipegfilgrastim off-label use as reported in a preceding feasibility study, indicating very high adherence to the approved indication.

Colony stimulating factors for prophylaxis of chemotherapy-induced neutropenia in children.

INTRODUCTION: Febrile neutropenia (FN) is one of the complications of chemotherapy that can increase the risk of infection and mortality. Granulocyte colony-stimulating factors (G-CSFs) are used in practice to prevent and treat episodes of neutropenia. The use of G-CSFs in children with cancer has not been studied much for primary prophylaxis of FN. AREAS COVERED: Current data suggest that G-CSFs have a similar pharmacokinetic profile in children and adults. Clinical trials published from 2002 to 2021 using G-CSFs in pediatric cancer patients were reviewed. All evaluated clinical trials used a dosage of 5 mcg/kg of filgrastim daily until neutrophil recovery or a single dose of 100 mcg/kg pegfilgrastim. Filgrastim demonstrated the benefit in decreasing the duration of fever, hospital stay, and antibiotic use in high-risk neuroblastoma patients. Pegfilgrastim showed similar efficacy in reducing the occurrence of FN and infections, with bone pain as an adverse effect. EXPERT OPINION: Filgrastim 5 mcg/kg/day or pegfilgrastim 100 mcg/kg single dose is appropriate when given at least 24 hours or after the chemotherapy in pediatric patients who weigh 45 kg or more. More prospective randomized trials are necessary to further investigate the efficacy and safety of G-CSFs in children with different types of cancer.

Induction of M-MDSCs with IL6/GM-CSF from adherence monocytes and inhibition by WP1066.

Peripheral blood monocytes acquire the phenotype of myeloid-derived suppressor cells (MDSCs) by induction of cytokine or co-culture with cancer cells and are widely used to model MDSCs for in vitro studies. However, the simplest method of plastic adhesive sorting is poorly described as the purity of monocyte resulting from this method is the lowest compared with flow cytometry cell-sorting and magnetic beads sorting. Therefore, the present study aimed at investigating the effect of the plastic adhesive monocyte isolation techniques on the resulting MDSCs phenotype. Monocytes were allowed to adhere for 1 h and cultured with IL6 and granulocyte-macrophage colony-stimulating factors (GM-CSF) for 7 days. Plastic adhesion sorting resulted in early low monocyte yield and purity, but high purity of MDSCs was obtained by refreshing the induction medium. The resulting MDSCs were the major subpopulation of CD33+CD11b+CD14+CD15-human leukocyte antigen (HLA)-/low cells and provided the potent capacity to suppress T cell proliferation and cytokine IFN-γ production. Moreover, the induced MDSCs were inhibited by STAT3 inhibitor WP1066, resulting in downregulation of phosphorylated-STAT3 and PD-L1 expression and upregulation of apoptosis respectively. In conclusion, the present study described the generation of monocytic MDSCs from adherence monocytes and the inhibition of STAT3 inhibitor WP1066 on the induced MDSCs. The present study contributed to the development of a new clinical drug, WP1066 targeting MDSC.

A retrospective review of the real-world experience of the Pegfilgrastim biosimilar (Lapelga®) to the reference biologic (Neulasta®).

INTRODUCTION: Cancer patients receiving myelosuppressive chemotherapy are vulnerable to febrile neutropenia (FN) which contributes to poor treatment outcomes. The use of granulocyte colony-stimulating factors is administered to prevent chemotherapy-induced neutropenia. The introduction of biosimilars has allowed for greater cost-savings while maintaining safety and efficacy. This retrospective study assessed the incidence of FN and related treatment outcomes and the cost minimization of a pegfilgrastim biosimilar and its reference. METHODS: A retrospective chart review of breast cancer patients receiving (neo) adjuvant chemotherapy from February 2017 to May 2020 was conducted. The endpoints included the incidence of FN, the occurrence of dose reduction (DR), dose delay (DD) and pain. A cost minimization analysis was performed from a third-party payer perspective. RESULTS: One hundred Neulasta® and 74 Lapelga® patients were included in the first-cycle analysis. The rate of FN in cycle 1 for Neulasta® and Lapelga® was 2/100 and 4/74, respectively; risk difference (RD) = 3.4%; 95% CI: -2.4 to 9.2%. Eighty-three Neulasta® and 59 Lapelga® patients were included in the all-cycle analyses, where DR was reported in 76 (15%) Neulasta® cycles vs 33 (10%) Lapelga® cycles (RD = -3.6, 95% CI: -10.2 to 2.9). DD was reported in 20 (4%) Neulasta® cycles vs. 11 (3.5%) Lapelga® cycles (RD = -0.3; 95% CI: -2.7 to 2.0). Adverse events were similar between groups. Cost minimization using a cohort of 20,000 patients translated into an incremental savings of $21,606,800 CAD for each cycle. CONCLUSION: The biosimilar pegfilgrastim was non-inferior to the reference biologic based on FN incidence in addition to related outcomes including DR and DD.

Cytokine Patterns in Maternal Serum From First Trimester to Term and Beyond.

Pregnancy implies delicate immunological balance between two individuals, with constant changes and adaptions in response to maternal capacity and fetal demands. We performed cytokine profiling of 1149 longitudinal serum samples from 707 pregnant women to map immunological changes from first trimester to term and beyond. The serum levels of 22 cytokines and C-reactive protein (CRP) followed diverse but characteristic trajectories throughout pregnancy, consistent with staged immunological adaptions. Eotaxin showed a particularly robust decrease throughout pregnancy. A strong surge in cytokine levels developed when pregnancies progressed beyond term and the increase was amplified as labor approached. Maternal obesity, smoking and pregnancies with large fetuses showed sustained increase in distinct cytokines throughout pregnancy. Multiparous women had increased cytokine levels in the first trimester compared to nulliparous women with higher cytokine levels in the third trimester. Fetal sex affected first trimester cytokine levels with increased levels in pregnancies with a female fetus. These findings unravel important immunological dynamics of pregnancy, demonstrate how both maternal and fetal factors influence maternal systemic cytokines, and serve as a comprehensive reference for cytokine profiles in normal pregnancies.

Efficacy and Safety of Filgrastim and Its Biosimilars to Prevent Febrile Neutropenia in Cancer Patients: A Prospective Study and Meta-Analysis.

Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrophil count ANC recovery, depth of ANC nadir (lowest ANC), neutropenia-related hospitalization and other neutropenia-related complications. For filgrastim versus biosimilar filgrastim comparison, the primary efficacy endpoint was the mean difference in duration of severe neutropenia DSN. Results: A total of 56 studies were considered that included data from 13,058 cancer patients. The risk of febrile neutropenia in filgrastim versus placebo/no treatment was not statistically different. The risk ratio for febrile neutropenia was 0.58, a 42% reduction in favor of filgrastim. The most reported adverse event with FIL was bone pain. For pegfilgrastim versus filgrastim, no statistically significant difference was noted. The risk ratio was 0.90 (95% CI 0.67 to 1.12). The overall difference in duration of severe neutropenia between filgrastim and biosimilar filgrastim was not statistically significant. The risk ratio was 1.03 (95% CI 0.93 to 1.13). Conclusions: Filgrastim was effective and safe in reducing febrile neutropenia and related complications, compared to placebo/no treatment. No notable differences were found between pegfilgrastim and filgrastim in terms of efficacy and safety. However, a similar efficacy profile was observed with FIL and its biosimilars.

A Simon's two-stage design trial evaluating the potential role of a kind of honey in preventing chemotherapy-hematopoietic toxicities.

BACKGROUND AND AIM: Hematopoietic toxicities are a serious consequence of myelosuppressive CT that may result in dose reductions, delays or even discontinuation of CT, which, in turn, may compromise patient outcomes. Concerns about tolerability and costs of CSFs are still ongoing, therefore the potential use of supportive therapeutics agents are still of interest. EXPERIMENTAL PROCEDURE: We performed a monocentric, phase II study using Simon's two-stage design. The primary endpoint was the evaluation of the potential clinical benefit of a special kind of honey (Life-Mel Honey) administered prophylactically to reduce the incidence of hematopoietic toxicities following chemotherapy. We have enrolled patients undergoing adjuvant or first-line chemotherapy. RESULTS AND CONCLUSION: From November 2013 to May 2014 (First stage) and from November 2014 to April 2016 (Second stage), 39 patients were enrolled at our Institution. The majority of patients was male (24/39, 61.5%), medium age was 60.4 years (range 34-77 years). The median follow up was 74.5 days (SD +/- 28.5). Overall, the majority of patients could underwent their chemoterapy with a regular schedule (25/39, 64.1%), while 9/39 patients (23.1%) need to delay chemotherapy due to hematological adverse events of various grade. Ten/39 patients (25.6%) had a grade 1 neutrophils count decreased, 56.4% a grade 1 platelets count decrease and 64.1% a grade 1 hemoglobin decrease. Therefore, Life-Mel Honey showed an interesting profile to reduce hematological toxicities. The proportion of responses is sufficiently high to recommend this honey to go to a next step in the clinical trial phase.

Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1.

Classically activated M1 macrophages and alternatively activated M2 macrophages are two polarized subsets of macrophages at the extreme ends of a constructed continuum. In the field of cancer research, M2 macrophage reprogramming is defined as the repolarization of pro-tumoral M2 to anti-tumoral M1 macrophages. It is known that colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) and CSF2/CSF2R signaling play important roles in macrophage polarization. Targeting CSF1/CSF1R for M2 macrophage reprogramming has been widely performed in clinical trials for cancer therapy. Other targets for M2 macrophage reprogramming include Toll-like receptor 7 (TLR7), TLR8, TLR9, CD40, histone deacetylase (HDAC), and PI3Kγ. Although macrophages are involved in innate and adaptive immune responses, M1 macrophages are less effective at phagocytosis and antigen presenting, which are required properties for the activation of T cells and eradication of cancer cells. Similar to T and dendritic cells, the "functionally exhausted" status might be attributed to the high expression of programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1). PD-L1 is expressed on both M1 and M2 macrophages. Macrophage reprogramming from M2 to M1 might increase the expression of PD-L1, which can be transcriptionally activated by STAT3. Macrophage reprogramming or PD-L1/PD-1 blockade alone is less effective in the treatment of most cancers. Since PD-L1/PD-1 blockade could make up for the defect in macrophage reprogramming, the combination of macrophage reprogramming and PD-L1/PD-1 blockade might be a novel treatment strategy for cancer therapy.

Long-term patient reported outcomes and hematologic toxicity among patients who received Granulocyte-Colony Stimulating Factors during chemotherapy for early breast cancer.

We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast cancer patients in CANTO (NCT01993498). Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use [95%CI]: +1.27 [-0.33 to +2.87] and -1.01 [-1.98 to -0.04], respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time.

Advances in the pharmacological management of neutropenia in solid tumors: the advent of biosimilars.

Introduction: Severe neutropenia and infections are potentially life-threatening complications of cytotoxic antineoplastic therapies and often require hospitalization with a severe economic impact. Furthermore, hematological toxicity frequently results in chemotherapy dose reductions and delays that could interfere with disease control.Areas covered: This review provides an overview of granulocyte colony-stimulating factors (G-CSFs) including pegylated molecules, as well as more recent biosimilar G-CSFs, focusing on the toxicity, pharmacokinetics, and efficacy of these compounds.Expert opinion: The administration of hematopoietic growth factors in primary and secondary prophylaxis of neutropenia is a standard supportive care measure. Recently, several biosimilars have been developed. The market for biosimilar agents seems to be increasing over time thanks to their similar effectiveness and safety, compared with their originators, but lower costs.

Phagocytosis and the antigen-processing abilities of macrophages derived from monocytes in spinal tuberculosis patients.

This study examined the hypothesis that there is an impairment of macrophageal function in spinal TB. We examined macrophageal functions in spinal TB patients. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of five spinal TB patients and five healthy persons as control. The isolated monocytes were cultured with stimulation of macrophage colony-stimulating factor (M-CSF) for seven days for maturation. The phagocytic ability of the macrophages derived from monocytes was measured. Also, nitric oxide (NO), myeloperoxidase (MPO), beta-glucuronide, and acid phosphatase activity was investigated. We found that the monocytes collected from patient PBMCs were significantly fewer than those of the control group (2992.103 vs. 6474.103 (cells/mL)). There were also fewer macrophages that had adhered to sheep red blood cells (SRBC) (598.103 vs. 264.103 (cells/mL)). However, NO production (2346 vs. 325.17 (µmol/gram of protein)), and the MPO (570.7 vs. 17.4 (unit/mg), beta-glucuronide (0.149 vs. 0.123 (µmol/hour/100 mg of protein)), and acid phosphatase activities (1776.9 vs. 287.9 (µmol/hour/100 mg of protein)) of the macrophages in the spinal TB group were markedly higher than in the healthy group. Despite the low adhesion to foreign bodies, the intracellular processing of TB macrophages, including oxidative activity and lysosome function, was significantly high. These results suggested the impairment of macrophageal function in spinal TB. Possibly, there is a dominance of innate non-specific immunity in spinal TB infection.

Protein and Small-Molecule Leucopoiesis and Thrombopoiesis Stimulators.

Pluripotent stem cells of the bone marrow are stimulated by different cytokines to proliferation and differentiation into various types of blood cells. These cytokines are mostly glycoproteins. Erythropoietin stimulates stem cells to the formation of erythrocytes while colony-stimulating factors cause the formation of different types of white blood cells. Stem cell factors play an important role in the maintenance and survival of blood cells of all types. Thrombopoietin stimulates stem cells to proliferation and formation of blood platelets. Granulocyte colony-stimulating factor is probably the most important drug in use. It stimulates stem cells to the formation of neutrophile granulocytes. It is often used in recombinant forms such as filgrastim in the treatment of neutropenia in cancer chemotherapy or AIDS. Its pegylated conjugates such as pegfilgrastim are also available. Its activity can be supported by plerixafor, a small molecule - bicyclam derivative acting as an indirect agonist of stem cells factor. It acts as an antagonist of CXCR4 receptor activation of which brakes hematopoiesis. The treatment of conditions accompanied by thrombocytopenia such as idiopathic thrombocytopenic purpura is currently not performed by thrombopoietin but synthetic agonists of its receptor are preferred. Romiplostim is a peptibody. It consists of a protein part interacting with the thrombopoietin receptor which is, however, different from thrombopoietin, and of Fc fragment of immunoglobulin G1. In contrast, small molecule thrombopoietin receptor agonists represented by eltrombopag can be given orally unlike all of the above.

Expression and significance of granulocyte colony-stimulating factor and granulocyte- macrophage colony-stimulating factor in patients with acute respiratory distress syndrome / 中国基层医药

Objective:To investigate the expression and significance of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute respiratory distress syndrome (ARDS).Methods:The clinical data of 81 patients with ARDS who received treatment between February 2018 and July 2020 in Linhai Second People's Hospital, China (group A) and 69 healthy controls who concurrently received physical examination (group B) were retrospectively analyzed. Serum levels of G-CSF, GM-CSF and oxygenation index (OI) measured before treatment in the group A were compared with the levels measured in the control group. Serum levels of G-CSF and GM-CSF measured before treatment were compared between patients with different disease severities in the group A. The correlation between serum G-CSF and GM-CSF levels and disease condition was analyzed. The significance of serum G-CSF and GM-CSF levels in the diagnosis of ARDS was investigated.Results:Before treatment, serum G-CSF and GM-CSF levels in the group A were (201.89 ± 19.44) ng/L, (48.95 ± 6.03) ng/L, respectively, which were significantly higher than those in the group B [(38.13 ± 5.22) ng/L, (7.71 ± 0.92) ng/L, t = 67.889, 56.228, both P < 0.001]. OI in the group A was significantly lower than that in the group B [(159.09 ± 16.81) mmHg vs. (385.13 ± 20.34) mmHg, t = 74.519, P < 0.001). In group A, serum levels of G-CSF and GM-CSF were (271.99 ± 23.15) ng/L and (65.07 ± 8.38) ng/L respectively in patients with severe acute respiratory distress syndrome ( n = 13), (203.14 ± 18.36) ng/L and (50.91 ± 7.18) ng/L respectively in patients with moderate acute respiratory distress syndrome ( n = 30), and (176.92 ± 15.98) ng/L and (41.89 ± 6.02) ng/L, respectively in patients with mild acute respiratory distress syndrome ( n = 38). There was significant difference among patients with severe, moderate and mild acute respiratory distress syndrome ( F = 133.201, 57.116, both P < 0.05). Serum levels of G-CSF and GM-CSF in group A were negatively correlated with OI ( r = -0.819, -0.824, both P < 0.05). The area under the receiver operating characteristic curve of serum levels of G-CSF and GM-CSF and their combination were 0.780 (95% CI: 0.628-0.933), 0.752 (95% CI: 0.590-0.913) and 0.912 (95% CI: 0.835-0.989), respectively. The Youden index was 0.686, 0.696 and 0.739, respectively. The area under the receiver operating characteristic curve and the Youden index of the combined detection of serum levels of G-CSF and GM-CSF were highest. Conclusion:Serum levels of G-CSF and GM-CSF in patients with ARDS were higher than those in healthy controls. Higher serum levels of G-CSF and GM-CSF led to more severe disease condition. Serum levels of G-CSF and GM-CSF in combination has a higher value in the diagnosis of ARDS than serum levels of G-CSF and GM-CSF alone.