Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions / 医学前沿

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

Systematic investigations of COVID-19 in 283 cancer patients

AbstractsO_ST_ABSBackgroundC_ST_ABSCancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and ParticipantsData of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. ResultsA total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. ConclusionsThis is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.

Impacts of alcohol dependence on the anticonvulsant effect of diazepam / 天津医药

Objective To study the impacts of alcohol dependence on the anticonvulsant effect of diazepam. Meth?ods Kunming mice (n=36) were divided into 3 groups (n=12 in each group), Alcohol Dependence Group(A group), Diaze?pam Group(D group)and Normal Saline Group(N group). A group received an intraperitoneal injection with a 0.2 mL dose of 0.8%alcohol in NS (normal saline) , while both D and N group received an injection with a 0.2 mL dose of NS without alco?hol , twice a day. Mice’s autonomic activities were monitored every day. After 7 days, the electroconvulsive experiment was performed. Both A and D group were given a weight-based dose of 0.05 mL/10 g of 0.05%diazepam via intraperitoneal injec? tion, while N group was given a 0.05 mL/10 g dose of NS. Before administration and after 15, 30, 60 min of administration, the convulsion threshold of each group was measured. Results The count of autonomic activity of mice in A group was less than that of mice in D and N group during the 2nd day to 6th day(P0.05). The convulsion threshold of mice in A group was higher than that of mice in D and N group before administration(P0.05). After 15 min of administration, the convulsion threshold of mice in D group was high?er than that of mice in A and N group(P0.05). Conclusion Alcohol dependence has anticon?vulsant effect. Alcohol dependence weakens the anticonvulsant effect of diazepam.

JAK2V617F mutant-positive polycythemia vera complicated with acute coronary syndrome:a report of 2 cases and literature review / 中华全科医师杂志

Objective To review the clinical features , diagnosis , prognosis and treatment of polycythemia vera ( PV) complicated with acute coronary syndrome ( ACS) .Methods The clinical data of 2 PV patients complicated with ACS admitted to Peking Union Medical College Hospital ( PUMCH ) were retrospectively analyzed and the recent literatures were reviewed .Results Case 1 was a 65-year old man who had been diagnosed PV with a positive JAK2V617F mutation 3 years ago.At presentation, the patient was suffering from recurrent angina pectoris , and coronary angiography revealed that there was a severe ( 80%) stenosis in the middle segment of left circumflex and a Xience V stent was implanted .After the percutaneous transluminal coronary intervention ( PCI ) , secondary prevention for coronary heart disease and hydroxyurea for PV were given and the patient has been followed up regularly for more than three years and he is going well.Case 2 is a 44-year old man who was diagnosed PV with a positive JAK 2 mutation 3 years ago and hydroxyurea, interferon, aspirin was prescribed.Then splenic infarction, thrombosis of splenic vein,regional portal hypertension , severe varices of fundus of stomach and upper gastrointestinal bleeding developed with him.Two months ago , an AMI of inferior wall occurred and the angiographic findings demonstrated an thrombotic lesion in the proximal segment of the right coronary artery with a moderate stenosis ( 60%);1 month ago an AMI of anterior wall developed and coronary angiography discovered that there were diffuse thrombus in the proximal segment of left anterior descending artery with a severe stenosis ( 90%) and a complete occlusion in the right coronary artery .After double antiplatelet therapy with anticoagulation therapy of warfarin was given , the patient recovered gradually .Conclusions PV complicated with ACS is relatively rare.According to recent studies, positive JAK2V617F mutation, leukocytosis, age >65 years and positive history of thrombosis are the most important predictors of cardiovascular events .Clinicians should design individualized treatment strategies for patients on the basis of clinical features , coronary angiography findings and complications .For those with thrombotic lesion in the coronary artery due to the hypercoagulative state caused by PV, it should be cautious to carry out a coronary revascularization treatment .