Development and Validation of a Nomogram for Predicting Prognosis to Immune Checkpoint Inhibitors Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy improved the prognosis of patients with non-small cell lung cancer (NSCLC); however, reliable prognostic biomarkers are lacking. We explored factors associated with prognosis and developed a predictive model. METHODS: We retrospectively analyzed 130 consecutive stage IIIA-IVB NSCLC patients treated with ICIs combined with chemotherapy. Cox univariate and multivariate proportional hazards regression analyses were used to identify prognostic factors associated with progression-free survival (PFS). A nomogram was developed based on key factors in the training cohort (n = 86) and evaluated in the validation cohort (n = 44). According to the nomogram-based total point scores, we divided patients into low- and high-risk groups. RESULTS: In the training cohort, bone metastases (p = 0.017) and an increased derived neutrophil-to-lymphocyte ratio (p = 0.018) were significantly associated with poor PFS, while smoking (p = 0.007) and programmed death-ligand 1 (PD-L1) ≥50% (p = 0.001) were associated with improved PFS. A nomogram based on these factors was developed to predict PFS at 3, 6, and 12 months. The C-index of the nomogram to predict PFS was 0.725 (95% CI: 0.711-0.739) in the training cohort and 0.688 (95% CI: 0.665-0.711) in the validation cohort. The area under the curve (AUC) exhibited an acceptable discriminative ability, and calibration curves demonstrated a consistency between the actual results and predictions. In the training cohort, the median PFS (mPFS) was 12.3 and 5.7 months in the low- and high-risk groups, respectively (p < 0.001). In the validation cohort, the mPFS was 12.6 and 6.2 months in the low- and high-risk groups, respectively (p = 0.021). CONCLUSIONS: A predictive nomogram was developed to help clinicians assess prognosis early for advanced NSCLC patients who received ICI plus chemotherapy.

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

[The Diagnostic Value of Endobronchial Ultrasound-guided Needle Aspiration Biopsy for Lung or Mediastinal Lymph Node Cancer and Tuberculosis].

OBJECTIVES: To determine the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing lung or mediastinal lymph node cancer and tuberculosis. METHODS: Clinical and pathological data of 553 patients who underwent EBUS-TBNA from January 2013 to September 2016 in West China Hospital of Sichuan University were reviewed. The sensitivity, specificity and accuracy of EBUS-TBNA for diagnosing lymph node tumor and tuberculosis of hilar and mediastinal lymph nodes were calculated. RESULTS: The sensitivity, specificity and accuracy of EBUS-TBNA in diagnosing hilar and mediastinal lymph node cancer were 89.2% (263/295), 100% (247/247) and 94.1% (510/542), respectively, compared with 70% (76/117), 97.2% (385/396) and 89.9% (461/513), respectively, for diagnosing tuberculosis identified though granulomatous biopsy. In the 102 cases with acid fast staining and TB-PCR, 63.7% accuracy (58/91), 90.9% (10/11) sensitivity and 66.7% (68/102) specificity were found for any positive findings from acid fast bacilli or TB-DNA. CONCLUSIONS: EBUS-TBNA has high sensitivity and specificity for diagnosing hilar and mediastinal tumor, which can be used in combination with acid fast staining and TB-PCR for diagnosing tuberculosis.

Noninvasive genotyping and monitoring of anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer by capture-based next-generation sequencing.

Noninvasive genotyping of driver genes and monitoring of tumor dynamics help make better personalized therapeutic decisions. However, neither PCR-based assays nor amplicon-based targeted sequencing can detect fusion genes like anaplastic lymphoma kinase (ALK) rearrangements in blood samples. To investigate the feasibility and performance of capture-based sequencing on ALK fusion detection, we developed a capture-based targeted sequencing panel to detect and quantify rearrangement events, along with other driver mutation variants in plasma. In this perspective study, we screened 364 patients with advanced non-small cell lung cancer (NSCLC) for ALK rearrangements, and collected blood samples from 24 of them with confirmed ALK rearrangements based on their tissue biopsies. ALK rearrangements were successfully detected in 19 of 24 patients at baseline with 79.2% (95% CI 57.9%, 92.9%) sensitivity and 100% (36/36) specificity. Among the 24 patients, we obtained longitudinal blood samples from 7 of them after either chemotherapy and/or Crizotinib treatment for disease monitoring. The by-sample detection rate of ALK rearrangements after treatment drops to 69.2% (9 of 13). In addition to detecting ALK rearrangements, we also detected 3 Crizotinib resistant mutations, ALK L1152R, ALK I1171T and ALK L1196M from patient P4. ctDNA concentration correlates with responses and disease progression, reflecting its ability as a biomarker. Our findings suggest capture-based sequencing can detect and quantify ALK rearrangements as well as other somatic mutations, including mutations mediated drug resistance, in plasma with high sensitivity, paving the way for its application in identifying driver fusion genes and monitoring tumor dynamics in the clinic.

Accuracy of the interferon-gamma release assay for the diagnosis of tuberculous pleurisy: an updated meta-analysis.

Background and Objectives. The best method for diagnosing tuberculous pleurisy (TP) remains controversial. Since a growing number of publications focus on the interferon-gamma release assay (IGRA), we meta-analyzed the available evidence on the overall diagnostic performance of IGRA applied to pleural fluid and peripheral blood. Materials and Methods. PubMed and Embase were searched for relevant English papers up to October 31, 2014. Statistical analyses were performed using Stata and Meta-DiSc. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV) and diagnostic odds ratio (DOR) were count. Summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize the overall diagnostic performance. Results. Fifteen publications met our inclusion criteria and were included in the meta analysis. The following pooled estimates for diagnostic parameters of pleural IGRA were obtained: sensitivity, 0.82 (95% CI [0.79-0.85]); specificity, 0.87 (95% CI [0.84-0.90]); PLR, 4.94 (95% CI [2.60-9.39]); NLR, 0.22 (95% CI [0.13-0.38]); PPV, 0.91 (95% CI [0.85-0.96]); NPV, 0.79 (95% CI [0.71-0.85]); DOR, 28.37 (95% CI [10.53-76.40]); and AUC, 0.91. The corresponding estimates for blood IGRA were as follows: sensitivity, 0.80 (95% CI [0.76-0.83]); specificity, 0.70 (95% CI [0.65-0.75]); PLR, 2.48 (95% CI [1.95-3.17]); NLR, 0.30 (95% CI [0.24-0.37]); PPV, 0.79 (95% CI [0.60-0.87]); NPV, 0.75 (95% CI [0.62-0.83]); DOR, 9.96 (95% CI [6.02-16.48]); and AUC, 0.89. Conclusions. This meta analysis suggested that pleural IGRA has potential for serving as a complementary method for diagnosing TP; however, its cost, high turn around time, and sub-optimal performance make it unsuitable as a stand-alone diagnostic tool. Better tests for the diagnosis of TP are required.

New ideas for teaching electrocardiogram interpretation and improving classroom teaching content.

BACKGROUND: Interpreting an electrocardiogram (ECG) is not only one of the most important parts of diagnostics but also one of the most difficult areas to teach. Owing to the abstract nature of the basic theoretical knowledge of the ECG, its scattered characteristics, and tedious and difficult-to-remember subject matter, teaching how to interpret ECGs is as difficult for teachers to teach as it is for students to learn. In order to enable medical students to master basic knowledge of ECG interpretation skills in a limited teaching time, we modified the content used for traditional ECG teaching and now propose a new ECG teaching method called the "graphics-sequence memory method." METHODS: A prospective randomized controlled study was designed to measure the actual effectiveness of ECG learning by students. Two hundred students were randomly placed under a traditional teaching group and an innovative teaching group, with 100 participants in each group. The teachers in the traditional teaching group utilized the traditional teaching outline, whereas the teachers in the innovative teaching group received training in line with the proposed teaching method and syllabus. All the students took an examination in the final semester by analyzing 20 ECGs from real clinical cases and submitted their ECG reports. RESULTS: The average ECG reading time was 32 minutes for the traditional teaching group and 18 minutes for the innovative teaching group. The average ECG accuracy results were 43% for the traditional teaching group and 77% for the innovative teaching group. CONCLUSION: Learning to accurately interpret ECGs is an important skill in the cardiac discipline, but the ECG's mechanisms are intricate and the content is scattered. Textbooks tend to make the students feel confused owing to the restrictions of the length and the format of the syllabi, apart from many other limitations. The graphics-sequence memory method was found to be a useful method for ECG teaching.

Clinical significance of airway mucus hypersecretion in chronic obstructive pulmonary disease.

Airway mucus hypersecretion is one of the most important features of chronic obstructive pulmonary disease (COPD). Airway mucus hypersecretion in COPD patients results in outcomes such as rapid decline of lung function, poor quality of life, and high rate of acute exacerbation, hospitalization and mortality. Nonpharmacologic treatments for airway mucus hypersecretion in COPD include smoking cessation and physical rehabilitation. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. Novel drugs with promising prospects are currently under clinical trials.