Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction ...Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.展开更多
Clinical guidelines recommend a steady-state vancomycin(VCM)trough concentration(SVTC)of 10–15 mg/L for regular infections and 15–20 mg/L for severe infections.However,clinical trials have shown that increasing SVTC...Clinical guidelines recommend a steady-state vancomycin(VCM)trough concentration(SVTC)of 10–15 mg/L for regular infections and 15–20 mg/L for severe infections.However,clinical trials have shown that increasing SVTC is not beneficial for efficacy,and instead it leads to nephrotoxicity.To verify whether increasing the SVTC results in improved clinical outcomes with sustainable adverse effects,we prospectively determined its correlation with clinical efficacy and safety.The participants included patients hospitalized with Gram-positive bacterial infections from March 2017 through October 2018.The patients were classified into group I(SVTC<10 mg/L),II(10≤SVTC≤20 mg/L),or III(SVTC>20 mg/L).Clinical,microbiological,and laboratory data were collected.Clinical outcomes between group I and II were matched after propensity score matching(PSM).A total of 331 patients were included in this study.Clinical failure occurred in 59(29%)of 204 patients on day 14,with no significant difference between groups I and II(P=0.535).Infection recurred at 28 d in 62(30%)of 204 patients,and no significant difference in infection recurrence was observed between both the groups(log-rank,P=0.674).Except for a significant increase in the incidence of acute kidney injury in group II,no significant difference was observed between two groups for any clinical results.The incidence of adverse events in groups I and II was significantly lower than that in group III(P<0.001).SVTC had an applicable cut-off point at 14.55 mg/L.SVTC was not correlated with VCM clinical efficacy,while it was a good indicator of nephrotoxicity.展开更多
文摘Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 （PD-1） and its ligand （PD-L1）, have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer （NSCLC）. Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry （IHC） with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-I/PD-L1 pathway.
基金Fujian Medical Innovation Project(Grant No.2017-CX-31)Guidance Project of Fujian Science and Technology Department(Grant No.2017Y0033).
文摘Clinical guidelines recommend a steady-state vancomycin(VCM)trough concentration(SVTC)of 10–15 mg/L for regular infections and 15–20 mg/L for severe infections.However,clinical trials have shown that increasing SVTC is not beneficial for efficacy,and instead it leads to nephrotoxicity.To verify whether increasing the SVTC results in improved clinical outcomes with sustainable adverse effects,we prospectively determined its correlation with clinical efficacy and safety.The participants included patients hospitalized with Gram-positive bacterial infections from March 2017 through October 2018.The patients were classified into group I(SVTC<10 mg/L),II(10≤SVTC≤20 mg/L),or III(SVTC>20 mg/L).Clinical,microbiological,and laboratory data were collected.Clinical outcomes between group I and II were matched after propensity score matching(PSM).A total of 331 patients were included in this study.Clinical failure occurred in 59(29%)of 204 patients on day 14,with no significant difference between groups I and II(P=0.535).Infection recurred at 28 d in 62(30%)of 204 patients,and no significant difference in infection recurrence was observed between both the groups(log-rank,P=0.674).Except for a significant increase in the incidence of acute kidney injury in group II,no significant difference was observed between two groups for any clinical results.The incidence of adverse events in groups I and II was significantly lower than that in group III(P<0.001).SVTC had an applicable cut-off point at 14.55 mg/L.SVTC was not correlated with VCM clinical efficacy,while it was a good indicator of nephrotoxicity.
