ABSTRACT
Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancer (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/geneticsABSTRACT
Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.
ABSTRACT
Objective@#To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.@*Methods@#A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.@*Results@#The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group.@*Conclusions@#Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.
ABSTRACT
Objective To investigate the distribution of occupations and traditional Chinese medical syndromes of the patients with hypokalemic periodic paralysis in Foshan area. Methods A multicenter retrospective investigation was carried out to analyze the characteristics of occupations and syndrome types of hypokalemic periodic paralysis in Foshan area, and the correlation of occupations with syndrome types was also explored. Results (1) The workers engaged in agriculture, forestry, animal-breeding and fishing, and the workers engaged in production & transportation were most likely to suffering from hypokalemic periodic paralysis, with the incidence being 36.8%, 34.7% respectively. (2) The damp-heat syndrome was the most commonly-seen syndrome type, accounting for 53.1%, and then followed by Qi deficiency syndrome (20.3%) and Qi-Yin deficiency syndrome(15.7%).(3) The syndromes of heavy manual labor workers such as agriculture, forestry, animal-breeding and fishing workers, production & transportation workers, and soldiers were characterized by damp-heat type, accounting for 62.5%, 69.4%, 47.0% respectively. Professionals & technicians were most likely to suffering from Qi-Yin deficiency syndrome, accounting for 44.4%; business service personnel were most likely to suffering from Qi-Yin deficiency syndrome (32.5%) and Qi deficiency syndrome (31.3%). The syndrome distribution of heavy manual labor workers differed from that of light manual labor workers and brain workers(P < 0.001). Conclusion The high-risk groups of hypokalemic periodic paralysis in Foshan area are the heavy manual labor workers who are manifested with the damp-heat syndrome. The dominated syndrome types of light manual labor workers and brain workers are Qi deficiency and Qi-Yin deficiency.