NEJM: Targeted drugs are effective for cancer patients with specific mutations

According to the latest results of a phase 2 clinical trial, a targeted therapy called capatinib can bring important things to patients with advanced lung cancer with specific genetic mutations. The trial was conducted by an international team led by researchers at Massachusetts General Hospital (MGH), and the trial was published in the New England Journal of Medicine. A protein called MET affects various processes in cells. Changes in the MET gene that activates this protein are related to many cancers. Multiple copies of the MET gene occur in 1-6% of patients with non-small cell lung cancer (NSCLC), that is, MET amplification. Deletion mutations in MET exon 14 will result in the deletion of related regions in the expressed protein. About 3-4% of NSCLC patients have these mutations, and the prognosis is poor. Capatinib is a highly effective and selective MET inhibitor. Now, researchers report the results of the Phase 2 GEOMETRYmono-1 study, which investigated the activity of capatinib in 364 advanced NSCLC patients with MET exon 14 mutations or MET amplification. In patients with mutations in exon 14 of MET, capatinib has a high response rate (68%) as a first-line treatment, while patients receiving other therapies (for example, chemotherapy and immunotherapy. In patients with at least 10 genes) In patients with copies of MET amplification, the response rate of capatinib to first-line treatment was 40%, and the response rate after other treatments was 29%. The drug has limited efficacy in patients with low levels of MET amplification. The results show that, For NSCLC patients with MET exon 14 mutations and those who have not been previously treated, capatinib may be a particularly effective treatment. “There are many advances in the treatment of non-small cell lung cancer, which can help people It is very important to live longer and better lives, and that all newly diagnosed patients with non-small cell lung cancer should receive extensive molecular profiling to determine their best first-line treatment.” Senior author, Harvard Medical School Said RebeccaSukHeist, associate professor of Medicne.

What is the cause of aortic stenosis?

 What is aortic stenosis? Is it seriously life-threatening if I have the disease? In fact, this disease is a type of heart disease. This disease is caused by congenital or acquired factors that cause aortic valve lesions that cause the aortic valve to not fully open during systole.  Aortic valve stenosis can be caused by a variety of reasons. The causes of aortic valve stenosis are mainly caused by the sequelae of rheumatic fever, congenital aortic valve structural abnormalities or senile aortic valve calcification. Congenital malformations are often caused by an abnormal number of leaflets, and the two-leaf type is the most common. Rheumatic valvular disease usually has both stenosis and insufficiency. Acquired non-rheumatic valve disease is mainly degenerative aortic valve sclerosis in the elderly, often accompanied by extensive atherosclerosis or hypercholesterolemia. The disease often develops slowly and has a long asymptomatic period, but the prognosis is poor, and the condition will deteriorate rapidly after heart failure. Aortic valve stenosis is caused by chronic recurrent rheumatic fever that causes swelling of the aortic valve annulus, fusion adhesion at the junction, contraction and stiffness of the free edge of the valve tip, and calcified nodules can be produced on the surface of the valve leaflets, causing the valve orifice narrow. These pathological changes often cause stenosis and reflux to coexist. Rheumatic aortic valve disease is often accompanied by mitral valve disease. ① In the decompensated period, due to the increased left ventricular systolic pressure, the left ventricular weight index increases and the myocardial oxygen consumption is at a high level, so obvious aortic valve stenosis can produce increased myocardial oxygen demand on the one hand, and on the other hand, due to the coronary The relative decrease in pulse flow leads to insufficient oxygen supply, which leads to ischemia of the subendocardial myocardium. When myocardial contractility is decompensated and weakened, left heart function declines. Finally, as myocardial degeneration decreases, the left ventricle dilates and the ejection fraction decreases. As a result, the left ventricular end-diastolic pressure further increased leading to pulmonary venous hypertension, resulting in chronic pulmonary congestion. Aortic valve stenosis increases myocardial oxygen demand and subendocardial perfusion pressure, which can cause arrhythmia, chest pain, and even sudden cardiac death. Adults can also be accompanied by coronary heart disease and aggravate myocardial ischemia. Long-term pulmonary congestion can gradually produce pulmonary hypertension, resulting in right ventricular hypertrophy and dilation, which ultimately leads to right heart failure. ②The left atrial ventricular compensation period is about 3.0cm2, and when the orifice area is reduced to 1.0cm2, the left ventricular blood flow is blocked and the systole is overloaded, resulting in a larger space between the left ventricle and the aorta Systolic pressure step difference, normal pressure step difference is 0.67 kPa (5 mm Hg), mild stenosis is 0.67 to 2.67 kPa (5 to 20 mm Hg), moderate stenosis is 2.67 to 6.67 kPa ( 20 to 50 mm Hg), more than 6.67 kappa (50 mm Hg) in severe stenosis (equivalent to the valve area reduced to less than a quarter of the normal, that is, the valve opening is less than 0.8 cm2). As the aortic valve stenosis worsens, the left ventricular concentric hypertrophy compensates for the increased pressure in the left ventricular cavity.  About the cause of aortic valve stenosis, we have learned through a brief introduction of the above related knowledge. At the same time, after learning the relevant disease knowledge, we must pay attention to our body in daily life, try not to be entangled by the terrible disease, affecting normal life.

What is the cause of aortic stenosis?

What is aortic stenosis? Is it seriously life-threatening if I have the disease? In fact, this disease is a type of heart disease. This disease is caused by congenital or acquired factors that cause aortic valve lesions that cause the aortic valve to not fully open during systole. According to medical research, the aortic valve stenosis can be caused by many reasons. The causes of aortic valve stenosis are mainly caused by the sequelae of rheumatic fever, congenital aortic valve structural abnormalities or senile aortic valve calcification. Congenital malformations are often caused by an abnormal number of leaflets, and the two-leaf type is the most common. Rheumatic valvular disease usually has both stenosis and insufficiency. Acquired non-rheumatic valve disease is mainly degenerative aortic valve sclerosis in the elderly, often accompanied by extensive atherosclerosis or hypercholesterolemia. The disease often develops slowly and has a long asymptomatic period, but the prognosis is poor, and the condition will deteriorate rapidly after heart failure. Aortic valve stenosis is caused by chronic recurrent rheumatic fever that causes swelling of the aortic valve annulus, fusion adhesion at the junction, contraction and stiffness of the free edge of the valve tip, and calcified nodules can be produced on the surface of the valve leaflets, causing the valve orifice narrow. These pathological changes often cause stenosis and reflux to coexist. Rheumatic aortic valve disease is often accompanied by mitral valve disease. ① In the decompensated period, due to the increased left ventricular systolic pressure, the left ventricular weight index increases and the myocardial oxygen consumption is at a high level, so obvious aortic valve stenosis can produce increased myocardial oxygen demand on the one hand, and on the other The relative decrease in pulse flow leads to insufficient oxygen supply, which leads to ischemia of the subendocardial myocardium. When myocardial contractility is decompensated and weakened, left heart function declines. Finally, as myocardial degeneration decreases, the left ventricle dilates and the ejection fraction decreases. As a result, the left ventricular end-diastolic pressure further increased leading to pulmonary venous hypertension, resulting in chronic pulmonary congestion. Aortic valve stenosis increases myocardial oxygen demand and subendocardial perfusion pressure, which can cause arrhythmia, chest pain, and even sudden cardiac death. Adults can also be accompanied by coronary heart disease and aggravate myocardial ischemia. Long-term pulmonary congestion can gradually produce pulmonary hypertension, resulting in right ventricular hypertrophy and dilation, which ultimately leads to right heart failure. ②The area of ​​the normal aortic valve in the left ventricular compensation stage is about 3.0cm2. When the valve area is reduced to 1.0cm2, the left ventricular blood flow is blocked and the systolic load is excessive, resulting in a greater contraction between the left ventricle and the aorta Stage pressure gradient, normal pressure gradient 0.67 kPa (5 mm Hg), mild stenosis 0.67 to 2.67 kPa (5 to 20 mm Hg), moderate stenosis 2.67 to 6.67 kPa (20 To 50 mm Hg), more than 6.67 kappa (50 mm Hg) in severe stenosis (equivalent to the valve area reduced to less than a quarter of the normal, that is, the valve opening is less than 0.8 cm2). As the aortic valve stenosis worsens, the left ventricular concentric hypertrophy compensates for the increased pressure in the left ventricular cavity. About the cause of aortic valve stenosis, we have learned through a brief introduction of the above related knowledge. At the same time, after learning the relevant disease knowledge, we must pay more attention to our bodies in daily life, try not to be entangled by terrible diseases, and affect normal life.