Role of colony-stimulating factor in myelopoiesis in murine long-term bone marrow cultures

Weekly medium change or midweek feeding of long-term bone marrow cultures (LTMBCs) results in a significant increase in total myeloid cell production. Proliferative myeloid cells peak 48 hours after feeding, and nonproliferative myeloid cells reach maximum levels at 72 hours. This increase in myelopoiesis is invariably preceded by a significant elevation in biologically and immunologically measurable colony-stimulating factor (CSF) in the supernatants of LTBMC. The level peaks 24 hours after medium change, then gradually returns to basal values. The decrease in CSF relates to its consumption by generating myeloid precursors because no fluctuation in the levels occur in cultures without active myelopoiesis. No significant inhibitors or promoters of CSF were detected. When highly purified L cell CSF, CSF in lung-conditioned medium, or CSF concentrated from LTBMC supernatant is added to cultures, an identical increase in myelopoiesis occurs. Anti- CSF antiserum, added to culture at the time of medium change, totally neutralizes supernatant CSF levels but does not affect myelopoiesis. These findings suggest a potential regulatory role for CSF in myelopoiesis in LTBMC. CSF appears to function within the microenvironment through a mechanism involving cell:cell interactions or by causing the production of other substances that stimulate myelopoiesis. Because exogenous CSF stimulates myelopoiesis, it is likely that it too can react either directly or through microenvironmental cells to stimulate primitive myeloid cells to divide.     

Identification of a growth factor for primary murine stroma as macrophage colony-stimulating factor

Knowledge of the stromal microenvironment is crucial for understanding the hematopoietic system. We took advantage of an assay that permits analysis of primary stroma-initiating cells (SICs) on the clonal level, and further characterized SICs and the factors that regulate SICs. Stroma formation in this assay is dependent on a high-molecular-weight factor secreted by the stromal cell line AC3.U. Here we show that this factor is identical to macrophage colony-stimulating factor (M-CSF), and that purified M-CSF is sufficient for induction of stroma formation. M-CSF, isolated from the line AC3.U, as well as from L929 cells and COS cells transfected with an expression vector encoding M- CSF, migrated in two peaks as 160- and 650-kD species after gel filtration. These molecular-weight species encompassed all stroma- inducing activity, and both stimulated macrophage colony formation. Affinity chromatography and blocking studies with antibodies specific for M-CSF and c-fms confirmed M-CSF as the sole factor in the supernatant of the stromal cell line AC3.U that promotes stroma formation. Culture of marrow, for as little as 1 week, depleted M-CSF- dependent SIC while increasing the incidence of replatable, factor- independent SIC. This suggests that culture changes the properties of SICs, perhaps by inducing differentiation into mature stromal cells. Thus, our results show a novel function of M-CSF as an important modulator of stroma formation.     

Severe low-titer cold-hemagglutinin disease responsive to steroid pulse therapy

We report the case of a 12-year-old boy suffering from severe low-titer cold-hemagglutinin disease with excruciating colicky abdominal pain, jaundice, and acute hemolytic anemia requiring transfusion. Cold hemagglutinins of the IgM type and a positive direct antiglobulin test, predominantly against C3d, were found. Steroid pulse therapy with 20 mg/kg body wt. methylprednisolone for 3 consecutive days was given. Abdominal pain disappeared within 12 h of the first steroid infusion and hemolysis was halted. We conclude that a therapeutic trial with steroid pulse therapy in severe low-titer cold-hemagglutinin disease is warranted.     

超声双重造影在不同部位胃癌术前T分期及Borrmann分型中的应用价值比较

目的 比较超声双重造影在不同部位胃癌术前T分期及Borrmann分型中的应用价值。方法 选取我院91例胃癌患者的术前超声双重造影检查资料，进行回顾性分析。按胃癌发生部位分成分成胃上、中、下部癌，通过超声双重造影对不同部位胃癌进行术前定位、T分期和Borrmann分型，与病理结果对照。结果 超声双重造影对胃癌术前定位的符合率为94.51%；对胃癌术前T分期和Borrman分型的总体符合率分别为69.23%和85.92%。超声双重造影在胃下部癌术前T分期 (Kappa=0.75)与病理一致性较好，在胃上部和胃中部癌术前T分期(Kappa=0.49、Kappa=0.67）与病理一致性中等，在胃上部和胃下部癌术前Borrmann分型（Kappa=0.92、Kappa=0.78）与病理一致性较好，在胃中部癌术前Borrmann分型(Kappa=0.68）与病理一致性中等。结论 超声双重造影对胃癌术前定位、总体T分期和总体Borrmann分型的评估准确性均较好，在不同部位胃癌术前T分期和Borrmann分型诊断中存在差异。临床医师可根据需要选用此项检查。     

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aimWe aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH).Materials and methods Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) “uncontrolled” [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) “controlled” [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system.Results There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status.Conclusion In this study, the CIMT values of CAH cases were similar to those of healthy subjects.     

Risk factors associated with mortality in ıntensive care COVID-19 patients: the importance of chest CT score and intubation timing as risk factors

Background/aim Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the predictors of mortality in critically ill patients admitted to the intensive care unit (ICU) are not yet well understood. In this study, we aimed to investigate the risk factors associated with ICU mortality in our hospital.Materials and methods In this single-centered retrospective study, we enrolled 86 critically ill adult patients with COVID-19 admitted to ICU of Dokuz Eylül UniversityHospital (İzmir, Turkey) between 18 March 2020 and 31 October 2020. Data on demographic information, preexisting comorbidities, treatments, the laboratory findings at ICU admission, and clinical outcomes were collected. The chest computerized tomography (CT) of the patients were evaluated specifically for COVID-19 and CT score was calculated. Data of the survivors and nonsurvivors were compared with survival analysis to identify risk factors of mortality in the ICU.Results The mean age of the patients was 71.1 ± 14.1 years. The patients were predominantly male. The most common comorbidity in patients was hypertension. ICU mortality was 62.8%. Being over 60 years old, CT score > 15, acute physiology and chronic health evaluation (APACHE) II score ≥ 15, having dementia, treatment without favipiravir, base excess in blood gas analysis ≤ –2.0, WBC > 10,000/mm³, D-dimer > 1.6 µg/mL, troponin > 24 ng/L, Na ≥ 145 mmol/L were considered to link with ICU mortality according to Kaplan–Meier curves (log-rank test, p < 0.05). The APACHE II score (HR: 1.055, 95% CI: 1.021–1.090) and chest CT score (HR: 2.411, 95% CI:1.193–4.875) were associated with ICU mortality in the cox proportional-hazard regression model adjusted for age, dementia, favipiravir treatment and troponin. Howewer, no difference was found between survivors and nonsurvivors in terms of intubation timing.ConclusionsCOVID-19 patients have a high ICU admission and mortality rate. Studies in the ICU are also crucial in this respect. In our study, we investigated the ICU mortality risk factors of COVID-19 patients. We determined a predictive mortality model consisting of APACHE II score and chest CT score. It was thought that this feasible and practical model would assist in making clinical decisions.     

Clinical characteristics and risk factors for 28-day mortality in critically ill patients with COVID-19: a retrospective cohort study

BackgroundTo date, the coronavirus disease 2019 (COVID-19) caused more than 2.6 million deaths all around the world. Risk factors for mortality remain unclear. The primary aim was to determine the independent risk factors for 28-day mortality.Materials and MethodsIn this retrospective cohort study, critically ill patients (≥ 18 years) who were admitted to the intensive care unit due to COVID-19 were included. Patient characteristics, laboratory data, radiologic findings, treatments, and complications were analyzed in the study.ResultsA total of 249 patients (median age 71, 69.1% male) were included in the study. 28-day mortality was 67.9% (n = 169). The median age of deceased patients was 75 (66–81). Of them, 68.6% were male. Cerebrovascular disease, dementia, chronic kidney disease, and malignancy were significantly higher in the deceased group. In the multivariate analysis, sepsis/septic shock (OR, 15.16, 95% CI, 3.96–58.11, p < 0.001), acute kidney injury (OR, 4.73, 95% CI, 1.55–14.46,p = 0.006), acute cardiac injury (OR, 9.76, 95% CI, 1.84–51.83, p = 0.007), and chest CT score higher than 15 (OR, 4.49, 95% CI, 1.51-13.38, p = 0.007) were independent risk factors for 28-day mortality.ConclusionEarly detection of the risk factors and the use of chest CT score might improve the outcomes in patients with COVID-19.