Background Concurrent chemoradiotherapy (CCRT) is an optimal recommended treatment for stage III non‐small cell lung cancer (NSCLC). Herein, we aimed to investigate the efficacy and safety of oral vinorelbine plus cisplatin with concomitant radiotherapy for stage III NSCLC. Methods This prospective, open‐label, single‐arm, observational cohort study was performed between January 2010 and September 2016. Patients were treated with two cycles of chemotherapy with 60 mg/m 2 intravenous cisplatin on day 1 and 50 mg/m 2 oral vinorelbine on days 1, 8, and 15; radiotherapy was administered concurrently from day 1 when chemotherapy was initiated. A total dose of 66–70 Gy radiotherapy was delivered in daily fractions of 2 Gy for 6.5–7 consecutive weeks. The tumor response was assessed after completing concomitant treatment. Results A total of 58 patients were enrolled and analyzed; 31 patients had stage IIIA NSCLC and 27 had stage IIIB NSCLC. After induction CCRT, 31 patients achieved an objective response (complete response in one and partial response in 30; the response rate was 53.4%). The median progression‐free survival was 6.73 months (95% confidence interval [CI], 5.42–7.91), duration of response was 12.30 months (95% CI, 5.59–19.01), and overall survival was 24.83 months (95% CI, 19.26–30.21). No treatment‐related mortality was observed, and neutropenia was the most common grade 3 and 4 treatment‐related toxicity (11 patients; 18.9%). Conclusions CCRT with the weekly regimen of oral vinorelbine plus triweekly cisplatin was effective and safe for stage III NSCLC.
Primary influenza pneumonia is characterized by fever, cough, progressive dyspnea, and even respiratory failure in severe cases. Acute respiratory distress syndrome (ARDS) due to influenza pneumonia is rare and is associated with a very high mortality rate. Most reported cases of primary influenza pneumonia were caused by influenza A virus. There are rare reports of influenza B pneumonia, and most of the cases have occurred in children with underlying disease. We report a case of ARDS associated with influenza B pneumonia in a 28-year-old man without underlying disease. The pathologic features of the open lung biopsy were consistent with diffuse alveolar damage. The patient received oseltamivir and methylprednisolone therapy, but oxygenation deteriorated, and the patient was refractory to prone position ventilation and high frequency oscillatory ventilation. Extracorporeal membrane oxygenation was used as a life-sustaining modality, but the patient developed ventilator-associated pneumonia and died. Although rarely found, influenza B pneumonia could develop in adults without underlying disease and cause refractory ARDS.
Previous research suggested that the dramatical decrease in CD8+ T cells is a contributing factor in the poor prognosis and disease progression of COVID-19 patients. However, the underlying mechanisms are not fully understood. In this study, we conducted Single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) analysis, which revealed a proliferative-exhausted MCM+FASLGlow CD8+ T cell phenotype in severe/critical COVID-19 patients. These CD8+ T cells were characterized by G2/M cell cycle arrest, downregulation of respiratory chain complex genes, and inhibition of mitochondrial biogenesis. CellChat analysis of infected lung epithelial cells and CD8+ T cells found that the galectin signaling pathway played a crucial role in CD8+ T cell reduction and dysfunction. To further elucidate the mechanisms, we established SARS-CoV-2 ORF3a-transfected A549 cells, and co-cultured them with CD8+ T cells for ex vivo experiments. Our results showed that epithelial galectin-3 inhibited the transcription of the mitochondrial respiratory chain complex III/IV genes of CD8+ T cells by suppressing the nuclear translocation of nuclear respiratory factor 1 (NRF1). Further findings showed that the suppression of NRF1 translocation was associated with ERK-related and Akt-related signaling pathways. Importantly, the galectin-3 inhibitor, TD-139, promoted nuclear translocation of NRF1, thus enhancing the expression of the mitochondrial respiratory chain complex III/IV genes and the mitochondrial biogenesis of CD8+ T cells. Our study provided new insights into the immunopathogenesis of COVID-19 and identified potential therapeutic targets for the prevention and treatment of severe/critical COVID-19 patients.
To explore the metabolic changes and immune profiles in patients, we analyzed the data of patients with mild and severe COVID-19. Forty-seven percent (IQR, 33-59) of leukocytes were lymphocytes (2.5×109/L (IQR, 2.2-3.3)) and monocytes were 0.51×109/L (IQR, 0.45-0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45×109/L (IQR, 0.36-0.64). Twenty-one severe patients had low PO2 (57 mmHg (IQR, 50-73)) and SO2 (90% (IQR, 86-93)), and high lactate dehydrogenase (580 U/L (IQR, 447-696)), cardiac troponin I (0.07 ng/mL (IQR, 0.02-0.30)), and pro-BNP (498 pg/mL (IQR, 241-1726)). Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62-22.85) and 32.7 mg/L (IQR, 12.8-81.9), and a large number of RBC (46/μL (IQR, 4-242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose (7.4 mmol/L (IQR, 5.9-10.1)). Fifteen of 21 (71%) severe cases had urine glucose +, and 9 of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption. Severe cases had extraordinarily low serum uric acid (176 μmol/L (IQR, 131-256)). In the late stage of COVID-19, severe cases had extremely low CD4+ T cells and CD8+ T cells, but unusually high neutrophils (6.5×10⁹/L (IQR, 4.8-9.6)), procalcitonin (0.27 ng/mL (IQR, 0.14-1.94)), C-reactive protein (66 mg/L (IQR, 25-114)) and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and 2 of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) Ⅰ-Ⅲ, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.
Background and Aims: Most of the pure glass nodules (GGNs) ≤10 mm in diameter on computed tomography (CT) are considered as non-invasive adenocarcinoma.However, some of them are invasive adenocarcinomas (IAs).These cases should be treated differently in terms of surgery because they have different prognosis.Therefore, it is necessary to study the predictive factors for IA when pure GGN 10 mm or less in diameter is present.Methods: A retrospective study was conducted on the clinical data of 2261 patients with lung cancer who underwent surgical resection.We selected 450 patients of lung adenocarcinoma with pure ground-glass nodules 10 mm or less in diameter.We compared the clinical, surgical, and pathological characteristics of non-IA with those of IA.Results: Among the 450 patients, 14 (3.11%) were AAH, 228 (50.67%) were AIS, 182 (40.04%) were MIA, 26 (5.78%)wereIA.The age of the IA was older than the non-IA (60.19 vs 51.37 years; P < 0.001).The mean axial diameter of the GGN lesions in IA was larger than that in non-IA (8.02 vs 7.46 mm; P = 0.043).The mean density of CT value in IA was higher than that in non-IA (-514.15vs-606.24HU; P < 0.01).The IA had more EGFR mutation than non-IA (58.8% vs 29.7%; P = 0.02).Univariate logistic regression analysis identified the ag, unsmooth margin, axial size and mean density, EGFR mutation of GGNs as predictive factors for IA.Multivariate logistic regression analysis identified the age, unsmooth margin, axial size and mean density of GGNs as predictive factors for IA. Conclusion:The differences between IA and non-IA in age, lesion size, mean density and margin was significant.
According to the National Comprehensive Cancer Network (NCCN) guidelines, treatment plans for nonsmall cell lung cancer are to be based on cancer stage.Cancer staging for patients with resectable disease has been based on pathologic stage instead of preoperative clinical stage.However, the possibility of occult mediastinal lymph node metastases could lead to discrepancy between clinical and pathologic stage.While multi-modality treatments may be beneficial for patients with locally advanced disease, most studies have been based on clinical stage.The aim of this study was to identify the beneficial impact of neoadjuvant therapy and the prognostic value of final pathologic stage in these patients.This study enrolled 530 lung cancer patients who received anatomic resection and mediastinal lymph node dissection at Chang Gung Memorial Hospital from January 2005 through June 2011.All resected specimens were examined by pathologists.Postoperative adjuvant therapies were given according to NCCN guideline recommendations.The clinico-pathologic factors of these patients were collected and analyzed.Patients not receiving neoadjuvant therapy had a better probability of disease-free survival (P < 0.001) and overall survival (P ¼ 0.0005), as well as a lower incidence of early relapse.Patients not receiving neoadjuvant therapy had a better disease-free survival rate in stages IA (P < 0.001), IB (P ¼ 0.002), and IIB (P ¼ 0.0117) from the point of view of final pathologic stage.Patients receiving neoadjuvant therapy may experience a higher incidence of early relapse.Neoadjuvant therapy did not show definite benefits in the disease-free and overall survival rates from the point of view of final pathologic stage.Pathologic stage of nonsmall cell lung cancer patients who presented with resectable disease after neoadjuvant therapy did not predict the prognosis.(Medicine 94(40):e1700)
Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.
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