Development and Internal Validation of a Nomogram Used to Predict Chemotherapy-Induced Neutropenia in Non-Small Cell Lung Cancer Patients: A Retrospective Cohort Study.

PURPOSE: This study was designed to develop a nomogram for predicting neutropenia caused by chemotherapy in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Information was collected from 376 patients between November 2017 and November 2020. The endpoint was chemotherapy-induced neutropenia (absolute neutrophil count <2×109/L). Logistic regression was performed to appraise the prognostic value of each potential predictor. Risk predictors from the final predictive model were used to generate a nomogram. C-index and calibration curve as well as decision curve analysis (DCA) was applied to evaluate model performance. RESULTS: The multivariate regression model ultimately included three predictors: previous radiotherapy, the current cycle of chemotherapy and neutrophil counts before current chemotherapy. A nomogram was developed and displayed better discrimination (with C-index of 0.875 in the development group and 0.907 in the validation group). Favorable consistency was shown between predicted probability and observed probability in the calibration curves. DCA illustrated that when the threshold probability was 8%-90%, the predictive model provided a net benefit relative to the intervention-all or the intervention-none strategy, indicating that the nomogram had favorable potential clinical utility. CONCLUSION: This nomogram will be an available tool to quantify the risk of neutropenia after chemotherapy in patients who suffer from NSCLC and deserves further external validation.

Development of a bead-based suspension array for the detection of pathogens in acute respiratory tract infections.

We developed a high-throughput bead-based suspension array for simultaneous detection of 20 respiratory tract pathogens in clinical specimens. Pathogen-specific genes were amplified and hybridized to probes coupled to carboxyl-encoded microspheres. Fluorescence intensities generated via the binding of phycoerythrin-conjugated streptavidin with biotin-labeled targets were measured by the Luminex 100 bead-based suspension array system. The bead-based suspension array detected bacteria in a significantly higher number of samples compared to the conventional culture. There was no significant difference in the detection rate of atypical pathogensatypical pathogens or viruses between the bead-based suspension array and real-time PCR. This technology can play a significant role in screening patients with pneumonia.

Comparison of Talaromyces marneffei Infection in Human Immunodeficiency Virus-positive and Human Immunodeficiency Virus-negative Patients from Fujian, China.

BACKGROUND: Talaromyces (Penicillium) marneffei (TM) is an emerging dimorphic human pathogenic fungus that is endemic to Southeast Asia. TM mostly occurs as an opportunistic infection in patients with human immunodeficiency virus (HIV). The objective of this study was to compare the clinical and laboratory parameters of patients with TM infections who were HIV-positive and HIV-negative and to assess therapies and outcomes. METHODS: This was a retrospective analysis of 26 patients diagnosed with disseminated TM infection from September 2005 to April 2014 at Fujian Provincial Hospital, China. RESULTS: Patients with TM infection tend to present with fever, weight loss, and anemia. The time from symptom onset to confirmed diagnosis was greater for HIV-negative patients (n = 7; median: 60 days, range: 14-365 days) than for HIV-positive patients (n = 19; median: 30 days, range: 3-90 days, Mann-Whitney U = 31.50, P= 0.041). HIV-negative patients were more likely to have dyspnea (57.1% vs. 5.3%, χ2 = 8.86, P= 0.010), low neutrophil count (Mann-Whitney U = 27.00, P= 0.029), high CD4 count (Mann-Whitney U = 0.00, P= 0.009), and high lymphocyte count (Mann-Whitney U = 21.00, P= 0.009). There were no significant differences in other demographic, clinical, or biochemical characteristics. Among all the patients, 12 HIV-positive patient and 1 HIV-negative patient received amphotericin and fluconazole treatment, 9 of whom improved, 1 died, 2 had kidney damage, 1 had hypokalemia due to exceeded doses. CONCLUSIONS: HIV-negative patients with TM infections tend to have a longer diagnostic interval, a higher percentage of dyspnea, higher levels of CD4 and lymphocytes, and lower neutrophil counts than TM infection in HIV-positive patients. Treatment programs with amphotericin and fluconazole are mostly effective.

Silencing of Livin inhibits tumorigenesis and metastasis via VEGF and MMPs pathway in lung cancer.

Livin, an inhibitor of apoptosis protein (IAP), is overexpressed in various cancers and decreases tumor sensitivity to chemotherapy and radiotherapy. However, the effect of Livin on lung adenocarcinoma metastasis and the specific mechanism involved remain unclear. RNAi technology was used to stably silence Livin in A549 cells in the present study. The effect of Livin on tumor growth and invasion was investigated in lung cancer cells in vitro and animal models were established to determine the anti-metastasis ability of Livin silencing in vivo. The results indicated that Livin knock-down suppressed cell proliferation and inhibited cell invasion, accompanied by downregulation of VEGF and MMP-2/-9. Silencing of Livin resulted in the prevention of xenograft tumor formation. Seventy-five immunodeficient male BALB/C nude mice were randomly divided into three groups, the relative ratio of the areas with pulmonary nodules in the experimental group decreased from 46.71±7.27% to 11.07±2.94% compared with the negative control group (P<0.001), indicating the interaction between Livin, VEGF and MMPs. The xenograft tumor model of intravenous injection of tumor cells were successfully established and applied for the analysis of lung cancer tumorigenesis and metastasis in a time-dependent manner for the first time. Based on the reliable and reproducible animal model, our findings indicate that knock-down of Livin inhibits cell growth and invasion through blockade of the VEGF and MMPs pathways in lung cancer cells in vitro, and inhibits tumorigenesis and metastasis of lung cancer in vivo, suggesting that Livin is a promising antitumor target.

[A case-control study on the risk factors for lower respiratory tract infection by Stenotrophomonas maltophilia in a medical intensive care unit].

OBJECTIVE: To explore the risk factors for lower respiratory tract infection by Stenotrophomonas maltophilia in the medical intensive care unit (MICU) in Fujian Provincial Hospital. METHODS: A 1:4 matched case-control study was carried out in the MICU in Fujian Provincial Hospital. Thirty-five patients with hospital-acquired lower respiratory tract infection by Stenotrophomonas maltophilia from 2007 to 2010 were included as cases, and 140 patients without lower respiratory tract infection served as controls. The case group included 22 cases with respiratory diseases, 4 with cerebrovascular diseases, 4 with cardiovascular diseases, 1 with hemorrhage of the digestive tract, 1 with acute pancreatitis, 1 with chronic kidney disease, 1 with cervical cancer and 1 with Alzheimer's disease. While the control group included 30 cases with respiratory diseases, 44 with cerebrovascular diseases, 14 with cardiovascular diseases, 2 with malignant tumors and 50 with others. Patients' information, general situation before being admitted to MICU, drug therapy, invasive procedures and hospital-acquired infection were analyzed. Conditional logistic regression was performed to identify independent risk factors. RESULTS: Univariate analysis showed that factors such as more than 4 underlying diseases (OR = 4.63), APACHE-II score ≥ 20(OR = 10.29), stay in the general ward more than 1 week before being admitted to MICU, treatment with more than 3 kinds of antibiotics (OR = 8.03), endotracheal intubation (OR = 4.10) or tracheotomy (OR = 50.29) and mechanical ventilation (OR = 7.95) were risk factors for hospital-acquired lower respiratory tract infection by Stenotrophomonas maltophilia. Multivariate logistic regression showed that variables such as APACHE-II score (OR = 8.39), kinds of antibiotics used (OR = 5.96) and tracheotomy (OR = 28.92) were independent risk factors (P < 0.01). CONCLUSIONS: Underlying diseases, the severity of diseases, tracheotomy, mechanical ventilation, and the use of wide-spectrum antibiotics are important risk factors for lower respiratory tract infection by Stenotrophomonas maltophilia in MICU. To identify these factors and take preventive measures earlier may be useful for decreasing Stenotrophomonas maltophilia infection-related mortality.

Livin abrogates apoptosis of SPC-A1 cell by regulating JNKI signaling pathway.

Livin, a novel member of inhibitors of apoptosis protein, is highly expressed in tumor tissues. It is a potential target in tumor therapy. Silencing its gene expression has been found to promote tumor cell apoptosis or increase tumor sensitivity to therapies. This paper studied the effect of livin anti-apoptotic activity and examined its molecular mechanisms. In the study, higher levels of cell apoptosis were measured by FACS in the experiment group with livin expression silenced than that in controls (P < 0.05). After livin gene expression was knocked down, cleaved caspase-3 protein was up-regulated but caspase-3 mRNA expression was almost the same, the phosphorylated JNK1 protein was down-regulated but JNK1 mRNA and total JNK1 protein expression was approximately the same too. The results suggest that livin may exert anti-apoptotic action on SPC-A1 by activating JNK1 signaling pathway and inhibiting caspase-3 activation.