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Objective: To determine the effects of varying positive end-expiratory pressures (PEEPs) on right ventricular function, hemodynamics, oxygenation, and the incidence of acute cor pulmonale (ACP) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Methods: This prospective paired-design study involved patients with moderate-to-severe ARDS in the ICU. Participants received lung-protective ventilation and hemodynamic monitoring. During the study, mechanical ventilation was administered with PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, while maintaining an end-inspiratory plateau pressure ≤ 30 cmH2O. Various assessments, including transthoracic echocardiography, cardiac output measurement, and blood gas analysis, were conducted at baseline and after 1 h of ventilation at each PEEP. Subsequently, variations in ventilation oxygenation, echocardiographic parameters, and hemodynamic indicators under different PEEPs were analyzed to explore the potential effects of PEEP on right ventricular function and hemodynamics, as well as the incidence of ACP. Results: A total of 317 ARDS patients were screened. Among them, 104 met the diagnostic criteria for moderate-to-severe ARDS, and 52 completed the study. The baseline PEEP of these 52 participants, acquired before commencement, was 11.5 ± 1.7 cmH2O, and the incidence of ACP was 25.0% (13/52). Intensive care unit mortality, overall hospital mortality, and 28-day mortality rates were 19.2% (10/52), 21.2% (11/52), and 32.7% (17/52), respectively. During the study, ACP incidences at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O were 17.3% (9/52), 21.2% (11/52), and 38.5% (20/52), respectively. Meanwhile, the PaO2/FiO2 ratio improved with increasing PEEP, reaching 162.0 (140.9, 174.0), 171.0 (144.0, 182.0), and 176.5 (151.0, 196) mmHg at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, respectively. In addition, higher PEEPs were associated with a slight increase in PaCO2, showing statistically significant differences compared to moderate and low PEEPs. Compared to a PEEP of 5 cmH2O or 10 cmH2O, right ventricular function exhibited substantial changes at 15 cmH2O PEEP, manifested as increased pulmonary artery systolic pressure, enlarged right ventricular end-diastolic area, and decreased tricuspid annular plane systolic excursion, all with significant differences. Conversely, variations in left ventricular end-diastolic area and ejection fraction were not statistically significant. In terms of hemodynamics, increasing PEEP resulted in a decline in cardiac index (CI), with statistically significant differences between different PEEPs. Specifically, compared to the value at a PEEP of 5 cmH2O, the CI at a PEEP of 15 cmH2O decreased by 14.3% (2.63 [2.20, 2.95] vs. 3.07 [2.69, 3.67], p < 0.001). The decline in the stroke volume index with PEEP was more obvious (22.1 [18.4, 27.1] vs. 27.0 [24.2, 33.0], p < 0.001), reaching 18.1%. Additionally, both end-diastolic volume index and extravascular lung water index decreased significantly with increasing PEEP, while the pulmonary vascular permeability index remained unaffected. Conclusion: Different PEEPs can affect the incidence of ACP in patients with moderate-to-severe ARDS. High PEEP improves oxygenation and reduces extravascular lung water without significantly affecting the pulmonary vascular permeability index and left ventricular systolic function. Nevertheless, it can cause right ventricular dilation, as well as substantial declines in right ventricular systolic function and CI, thereby causing ACP.
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Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.
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Objective:To investigate the clinical value of neuron specific enolase (NSE) and bispectral index (BIS ) in predicting the neurological prognosis in patients with severe intracerebral hemorrhage.Methods:Patients with severe intracerebral hemorrhage admitted to the ICU of Xiaolan Hospital of Southern Medical University from January 2019 to December 2020 were selected, and serum NSE detection and BIS monitoring were performed at an early stage. According to the Glasgow outcome scale (GOS) at 90 days after intracerebral hemorrhage, the patients were divided into the good neurologic prognosis group (GOS 4-5) and poor neurologic prognosis group (GOS 1-3). The levels of NSE and BIS between the two groups were compared. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of NSE, BIS and their combination in predicting neurological prognosis.Results:A total of 126 patients with severe intracerebral hemorrhage were enrolled in this study, and 32 patients (25.4%) had poor neurological prognosis. The level of NSC in the poor neurological prognosis group was significantly higher than that in the good neurologic prognosis group [28 (13.7, 50.4) ng/mL vs. 13.5 (9.6, 18.5) ng/mL, P < 0.05], while the BIS level was significantly lower than that in the good neurologic prognosis group [32 (25.2, 45) vs. 55 (48, 62.2), P <0.05]. For detection of poor neurologic outcome in patients with severe intracerebral hemorrhage, NSE and BIS yielded the AUC values of 0.768 (0.685, 0.839) and 0.866 (0.793, 0.920), respectively, with cut-off values of 21.7 ng/mL and 47, respectively. The combination of NSE and BIS yielded a remarkably higher AUC value of 0.927 (0.867, 0.966) for predicting poor neurologic outcome than each index alone ( P<0.05). Conclusions:Early monitoring of NSE and BIS can effectively predict the neurological prognosis of patients with severe intracerebral hemorrhage, and the combination of NSE and BIS can further improve the prediction efficiency.
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Objective To evaluate the clinical efficacy and safety of capecitabine continuous maintenance in treatment of re-currence of triple-negative breast cancer,which had responded to combined chemoradiotherapy.Methods The triple-negative breast cancer was defined as negative of ER,PR and HER2.A total of 46 patients of triple-negative breast cancer were divided into the treatment group (23 patients)and the control group (23 patients).The treatment group was given capecitabine continuous mainte-nance after 6 cycles of chemotherapy.The control group was given 6 cycles of combined chemotherapy only.The clinical efficacy and safety was evaluated between the two groups.Results The PR,PD,RR,and DCR in the treatment group were significantly higher than those in the control group(P 0.05).Conclusion Capecitabine continuous maintenance after combined chemoradiotherapy in treatment of recurrence of triple-neg-ative breast cancer is more effective,lower toxicity and tolerable.
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or =70years of age) with advanced non-small-cell lung cancer. Single agent vinorelbine should be selective chemotherapy in elderly patients with advanced non-small-cell lung cancer.
