Effect of antibody-mediated connective tissue growth factor neutralization on lung edema in ventilator-induced lung injury in rats.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by alveolar edema that can progress to septal fibrosis. Mechanical ventilation can augment lung injury, termed ventilator-induced lung injury (VILI). Connective tissue growth factor (CTGF), a mediator of fibrosis, is increased in ARDS patients. Blocking CTGF inhibits fibrosis and possibly vascular leakage. This study investigated whether neutralizing CTGF reduces pulmonary edema in VILI. METHODS: Following LPS administration, rats were mechanically ventilated for 6 h with low (6 mL/kg; low VT) or moderate (10 mL/kg; mod VT) tidal volume and treated with a neutralizing CTGF antibody (FG-3154) or placebo lgG (vehicle). Control rats without LPS were ventilated for 6 h with low VT. Lung wet-to-dry weight ratio, FITC-labeled dextran permeability, histopathology, and soluble RAGE were determined. RESULTS: VILI was characterized by reduced PaO2/FiO2 ratio (low VT: 540 [381-661] vs. control: 693 [620-754], p < 0.05), increased wet-to-dry weight ratio (low VT: 4.8 [4.6-4.9] vs. control: 4.5 [4.4-4.6], p < 0.05), pneumonia (low VT: 30 [0-58] vs. control: 0 [0-0]%, p < 0.05) and interstitial inflammation (low VT: 2 [1-3] vs. control: 1 [0-1], p < 0.05). FG-3154 did not affect wet-to-dry weight ratio (mod VT + FG-3154: 4.8 [4.7-5.0] vs. mod VT + vehicle: 4.8 [4.8-5.0], p > 0.99), extravasated dextrans (mod VT + FG-3154: 0.06 [0.04-0.09] vs. mod VT + vehicle: 0.04 [0.03-0.09] µg/mg tissue, p > 0.99), sRAGE (mod VT + FG-3154: 1865 [1628-2252] vs. mod VT + vehicle: 1885 [1695-2159] pg/mL, p > 0.99) or histopathology. CONCLUSIONS: 'Double hit' VILI was characterized by inflammation, impaired oxygenation, pulmonary edema and histopathological lung injury. Blocking CTGF does not improve oxygenation nor reduce pulmonary edema in rats with VILI.

[The cause of anemia is underdiagnosed in primary care]. / Onderdiagnostiek naar anemie in de eerste lijn.

OBJECTIVE: To determine if general practitioners can diagnose the cause of anemia, based on the requested laboratory tests. DESIGN: Retrospective observational study. METHOD: The research population consisted of 20.004 adult patients with established anemia, who had blood samples analyzed by Atalmedial in 2019. The cause of anemia was found when criteria based on the NHG-standard were met. We considered the NHG-guideline to be followed when hemoglobin was requested in the first diagnostic request and when the correct combination of blood tests was requested in the second diagnostic request. Descriptive statistics and multilevel regression analysis were performed. RESULTS: A possible cause of anemia has been found in 38,7% of the patients within two diagnostic requests, regardless of the adherence to the NHG-guideline. The chance of finding a cause of anemia was smaller in men than women of the same age, whereas the chance was highest in women over the age of 80 and between 18 and 44. The NHG-guideline for anemia was followed in 11.794 (59%) of the patients in the first diagnostic request. 19,3% (11,4% of total) of these patients also had a second diagnostic request. In 10,4% (1,2% of total) of these patients, the NHG-guideline was adhered to in the second diagnostic request. CONCLUSION: A cause of anemia is, based on laboratory tests, often not diagnosed in daily practice in the primary care. The reason for this is insufficient laboratory follow-up after initial testing when no cause of anemia is found. The NHG-guideline for anemia is poorly adhered to.