BACKGROUND Immunotherapy plays an important role in advanced non-small cell lung cancer (NSCLC). However, radiological evaluation is challenging due to the potential inflammatory effects of immunotherapy, which can lead to atypical response patterns. Identifying these atypical responses is critical to making treatment decisions and prognostication. METHODS We performed a retrospective analysis of consecutive advanced NSCLC patients treated with immunotherapy (alone or in combination). We collected patients' clinical and pathological data, analyzed the proportion of patients who continued immunotherapy beyond progressive disease (PD) per RECIST 1.1, and compared the differences in response patterns between the RECIST 1.1 and iRECIST criteria. RESULTS A total of 43 patients treated at the Peking Union Medical College, China from January 2018 to April 2019 were included. Continued immunotherapy beyond PD per RECIST 1.1 was observed in 10 (33.3%, 10/30) patients, of which there were discordant assessments (30%, 3/10) between the RECIST 1.1 and iRECIST, which were evaluated as PD by RECIST 1.1 and immune unconfirmed PD by iRECIST. Among seven patients with immune confirmed PD, one (1/30, 3.3%) had pseudoprogression. Patients who continued immunotherapy beyond PD (n = 10) experienced significantly prolonged overall survival (not reached vs. 8.1 months hazard ratio, 2.8; 95% confidence interval 2.7-13.6, P = 0.03) compared with patients who did not continue immunotherapy beyond PD (n = 20). CONCLUSIONS RECIST 1.1 evaluation underestimated the benefit of immunotherapy. Further research is required to optimize iRECIST and establish some criteria for selecting patients who will benefit from continued immunotherapy beyond PD per RECIST 1.1. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.AIM High-altitude pulmonary oedema (HAPE) is a non-cardiogenic pulmonary oedema that can occur during rapid ascent to a high-altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary oedema rather than as a causative factor. In this study, we aim to understand the role of hypoxic response in myeloid cells and its involvement in pathogenesis of HAPE. METHODS We have generated a conditional deletion in **** of the von Hippel-Lindau factor (VHL) in myeloid cells to determine the effect of a deregulated hypoxic response in pulmonary oedema. RESULTS The deletion of VHL in pulmonary myeloid cells gave rise to pulmonary oedema, increased pulmonary vascular permeability and reduced performance during exertion. These changes were accompanied by reduced stroke volume in the left ventricle. CONCLUSION In this model, we show that a deregulated myeloid cell hypoxic response can trigger some of the most important symptoms of HAPE, and thus **** with a deletion of VHL in the myeloid lineage can function as a model of HAPE. © 2020 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.We introduce a new boron-doped cyclophane, the hexabora[16 ]cyclophane B6-F Mes, in which six tricoordinate borane moieties alternate with short conjugated p-phenylene linkers. Exocyclic 2,4,6-tris(trifluoromethyl)phenyl (F Mes) groups serve not only to further withdraw electron density but at the same time sterically shield the boron atoms, resulting in a macrocycle that is both highly electron-deficient and stable. The optical and electronic properties are compared with those of related linear oligomers and the electronic structure is further evaluated by computational methods. The studies uncover unique properties of B6-F Mes, including a low-lying and extensively delocalized LUMO and a wide HOMO-LUMO gap, which arise from the combination of a cyclic π-system, strong electronic communication between the closely spaced borons, and the attachment of electron-deficient pendent groups. The binding of small anions to the electron-deficient macrocycle and molecular model compounds is investigated and emissive exciplexes are detected in aromatic solvents. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Osimertinib is recommended for T790M mutation-positive advanced non-small cell lung cancer (NSCLC) resistant to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Recently, some reports exist on the real-world use of osimertinib; however, reports involving third/later-line use are few. Hence, this study was conducted to evaluate the efficacy and safety of osimertinib used in various treatment lines for T790M-positive NSCLC patients. METHODS This retrospective, observational, multicenter study included T790M-positive advanced/recurrent NSCLC patients treated with osimertinib from May 2016 to March 2018. https://www.selleckchem.com/products/n-acetyl-dl-methionine.html The clinical characteristics, efficacy, and adverse events were retrospectively investigated. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). PFS-associated clinical characteristics were evaluated using the Cox proportional hazards model. RESULTS The objective response rate (ORR) and disease coiously treated with EGFR-TKIs. However, the incidence of ≥ grade 3 adverse events, especially pneumonitis, was higher than that previously reported by other studies. What this study adds Osimertinib was approved for previously EGFR-TKI-treated EGFR T790M-positive NSCLC. With the increasing frequency of its use as first-line treatment, this study provides valuable evidence for the efficacy and safety of osimertinib for previously EGFR-TKI-treated NSCLC. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.BACKGROUND Neutrophil count reduction after chemotherapy has been related with longer survival of patients with metastatic pancreatic adenocarcinoma, but there is not a standardized measurement for this phenomenon. METHODS Some parameters related to the change in neutrophil count between the first and the second cycle of chemotherapy or between the baseline count and the nadir have been evaluated among patients with advanced pancreatic cancer at a single institution. A Cox regression model was built which included, in addition to the common prognostic variables, some variables related to the change of the neutrophil count after chemotherapy. RESULTS One hundred patients were selected. Two neutrophil kinetics related variables predicted overall survival independently, such as the neutrophil count growth rate (hazard ratio [HR] = 1.245; confidence intervals [CIs], 1.077-1.440) and the chemotherapy-induced neutropenia after one cycle (HR = 0.499; CIs, 0.269-0.927). CONCLUSION The kinetics of neutrophil count after chemotherapy is an early and independent prognostic factor, which appears to be simple to measure at the start of the second cycle of chemotherapy by means of the neutrophil count growth rate.
BACKGROUND Immunotherapy plays an important role in advanced non-small cell lung cancer (NSCLC). However, radiological evaluation is challenging due to the potential inflammatory effects of immunotherapy, which can lead to atypical response patterns. Identifying these atypical responses is critical to making treatment decisions and prognostication. METHODS We performed a retrospective analysis of consecutive advanced NSCLC patients treated with immunotherapy (alone or in combination). We collected patients' clinical and pathological data, analyzed the proportion of patients who continued immunotherapy beyond progressive disease (PD) per RECIST 1.1, and compared the differences in response patterns between the RECIST 1.1 and iRECIST criteria. RESULTS A total of 43 patients treated at the Peking Union Medical College, China from January 2018 to April 2019 were included. Continued immunotherapy beyond PD per RECIST 1.1 was observed in 10 (33.3%, 10/30) patients, of which there were discordant assessments (30%, 3/10) between the RECIST 1.1 and iRECIST, which were evaluated as PD by RECIST 1.1 and immune unconfirmed PD by iRECIST. Among seven patients with immune confirmed PD, one (1/30, 3.3%) had pseudoprogression. Patients who continued immunotherapy beyond PD (n = 10) experienced significantly prolonged overall survival (not reached vs. 8.1 months hazard ratio, 2.8; 95% confidence interval 2.7-13.6, P = 0.03) compared with patients who did not continue immunotherapy beyond PD (n = 20). CONCLUSIONS RECIST 1.1 evaluation underestimated the benefit of immunotherapy. Further research is required to optimize iRECIST and establish some criteria for selecting patients who will benefit from continued immunotherapy beyond PD per RECIST 1.1. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.AIM High-altitude pulmonary oedema (HAPE) is a non-cardiogenic pulmonary oedema that can occur during rapid ascent to a high-altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary oedema rather than as a causative factor. In this study, we aim to understand the role of hypoxic response in myeloid cells and its involvement in pathogenesis of HAPE. METHODS We have generated a conditional deletion in mice of the von Hippel-Lindau factor (VHL) in myeloid cells to determine the effect of a deregulated hypoxic response in pulmonary oedema. RESULTS The deletion of VHL in pulmonary myeloid cells gave rise to pulmonary oedema, increased pulmonary vascular permeability and reduced performance during exertion. These changes were accompanied by reduced stroke volume in the left ventricle. CONCLUSION In this model, we show that a deregulated myeloid cell hypoxic response can trigger some of the most important symptoms of HAPE, and thus mice with a deletion of VHL in the myeloid lineage can function as a model of HAPE. © 2020 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.We introduce a new boron-doped cyclophane, the hexabora[16 ]cyclophane B6-F Mes, in which six tricoordinate borane moieties alternate with short conjugated p-phenylene linkers. Exocyclic 2,4,6-tris(trifluoromethyl)phenyl (F Mes) groups serve not only to further withdraw electron density but at the same time sterically shield the boron atoms, resulting in a macrocycle that is both highly electron-deficient and stable. The optical and electronic properties are compared with those of related linear oligomers and the electronic structure is further evaluated by computational methods. The studies uncover unique properties of B6-F Mes, including a low-lying and extensively delocalized LUMO and a wide HOMO-LUMO gap, which arise from the combination of a cyclic π-system, strong electronic communication between the closely spaced borons, and the attachment of electron-deficient pendent groups. The binding of small anions to the electron-deficient macrocycle and molecular model compounds is investigated and emissive exciplexes are detected in aromatic solvents. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Osimertinib is recommended for T790M mutation-positive advanced non-small cell lung cancer (NSCLC) resistant to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Recently, some reports exist on the real-world use of osimertinib; however, reports involving third/later-line use are few. Hence, this study was conducted to evaluate the efficacy and safety of osimertinib used in various treatment lines for T790M-positive NSCLC patients. METHODS This retrospective, observational, multicenter study included T790M-positive advanced/recurrent NSCLC patients treated with osimertinib from May 2016 to March 2018. https://www.selleckchem.com/products/n-acetyl-dl-methionine.html The clinical characteristics, efficacy, and adverse events were retrospectively investigated. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). PFS-associated clinical characteristics were evaluated using the Cox proportional hazards model. RESULTS The objective response rate (ORR) and disease coiously treated with EGFR-TKIs. However, the incidence of ≥ grade 3 adverse events, especially pneumonitis, was higher than that previously reported by other studies. What this study adds Osimertinib was approved for previously EGFR-TKI-treated EGFR T790M-positive NSCLC. With the increasing frequency of its use as first-line treatment, this study provides valuable evidence for the efficacy and safety of osimertinib for previously EGFR-TKI-treated NSCLC. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.BACKGROUND Neutrophil count reduction after chemotherapy has been related with longer survival of patients with metastatic pancreatic adenocarcinoma, but there is not a standardized measurement for this phenomenon. METHODS Some parameters related to the change in neutrophil count between the first and the second cycle of chemotherapy or between the baseline count and the nadir have been evaluated among patients with advanced pancreatic cancer at a single institution. A Cox regression model was built which included, in addition to the common prognostic variables, some variables related to the change of the neutrophil count after chemotherapy. RESULTS One hundred patients were selected. Two neutrophil kinetics related variables predicted overall survival independently, such as the neutrophil count growth rate (hazard ratio [HR] = 1.245; confidence intervals [CIs], 1.077-1.440) and the chemotherapy-induced neutropenia after one cycle (HR = 0.499; CIs, 0.269-0.927). CONCLUSION The kinetics of neutrophil count after chemotherapy is an early and independent prognostic factor, which appears to be simple to measure at the start of the second cycle of chemotherapy by means of the neutrophil count growth rate.
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