Objective:To evaluate various blood lactate parameters in elderly patients with sepsis for prognostic prediction and exploration of optimal threshold values.The parameters include initial lactate concentration(LACinitial), lactate peak concentration(LACpeak), lactate peak time(LACtimetopeak), lactate accumulation area(LACarea), and 6-hour and 12-hour lactate clearance rates(LC_6 h and LC_12 h).Methods:This study conducted a retrospective screening of elderly patients with sepsis who were admitted to the intensive care unit(ICU)of the Beth Israel Deaconess Medical Center between 2008 and 2019.The study collected general information of the patients, as well as vital signs and laboratory indicators within 24 hours after admission.Additionally, the APSⅢ score, SOFA score, and OASIS score were continuously collected or calculated.The outcome variables examined were 28-day mortality from ICU admission, ICU length of stay, hospital length of stay, and mechanical ventilation time.The study compared the blood lactate parameters between the survival group and the nonsurvival group, and calculated the odds ratio( OR). A receiver operating characteristic curve(ROC curve)was plotted to analyze and compare the predictive performance of each lactate parameter based on 28-day mortality.The area under the curve(AUC)was calculated.Additionally, Kaplan-Meier survival curves were analyzed using the cutoff value of each lactate parameter. Results:A total of 4 773 elderly sepsis patients were included in the study.Among them, 1 166(24.4%)died within 28 days.The nonsurvival group had significantly higher levels of LACinitial[3.30(2.40, 5.30) vs.2.70(2.20, 3.50)mmol/L, Z=-13.047, P<0.001], LACarea[36.40(18.28, 63.00) vs.14.80(7.40, 27.30)mmol·L -1·h, Z=-10.298, P<0.001], LACpeak[4.00(2.80, 6.70) vs.3.10(2.50, 4.10)mmol/L, Z=-15.573, P<0.001], and LACtimetopeak[7.00(3.00, 15.00) vs.4.00(2.00, 8.00)h, Z=-13.084, P<0.001]. Additionally, the nonsurvival group had significantly lower levels of LC_6 h[0.06(-0.21, 0.29) vs.0.14(-0.22, 0.39), Z=2.966, P=0.003]and LC_12 h[0.12(-0.21, 0.42) vs.0.29(-0.09, 0.50), Z=5.638, P<0.001]. In this study involving 4 773 elderly sepsis cases, the lactate parameters were evaluated for their ability to predict death within 24 hours of ICU admission.The area under the curve(AUC)values, presented in descending order, were as follows: LACpeak[0.651(0.632, 0.670)], LACinitial[0.627(0.607, 0.646)], LACtimetopeak[0.626(0.607, 0.646)], and LACarea[0.590(0.569, 0.610)]. After excluding the cases where the LACarea was 0, the AUC increased to LACarea2[0.739(0.714, 0.764)]. A total of 1 217 patients had their lactate clearance rates at 6 hours and 12 hours calculated, with AUCs of LC_6 h[0.515(0.481, 0.548)]and LC_12 h[0.568(0.534, 0.603)], respectively.Furthermore, among 1 042 elderly sepsis patients with LACinitial>2 mmol/L, the AUCs of LC were LC_6 h[0.560(0.524, 0.596)]and LC_12 h[0.614(0.577, 0.651)]. The optimal cutoff values for LACinitial, LACpeak, LACtimetopeak, LACarea, LC_6 h, and LC_12 h, calculated from ROC curve analysis, were 3.55 mmol/L, 4.45 mmol/L, 7.50 h, 28.65 mmol·L -1·h, 0.304 and 0.272, respectively.The study population was divided into two groups based on whether they achieved the optimal cutoff value or not.The Kaplan-Meier survival curve showed a significant and distinguishable difference between these two groups(all P<0.05). Conclusions:In the prediction of 28-day mortality in elderly sepsis patients, LACarea was found to be the most effective indicator.LACpeak, LACinitial, and LACtimetopeak also showed acceptable predictive capabilities.On the other hand, LC performed the worst among the indicators, but its performance could potentially be enhanced by adjusting the applicable population.

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Receptor, ErbB-2/genetics* ; Mutation ; Antineoplastic Agents/pharmacology* ; Signal Transduction ; Protein Kinase Inhibitors/therapeutic use*