Novel insight from the first lung transplant of a COVID-19 patient.

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.

Serum Krebs von den Lungen-6 level as a diagnostic biomarker for interstitial lung disease in Chinese patients.

OBJECTIVES: The purpose of this study was to determine the diagnostic and prognostic values of serum KL-6 levels in Chinese patients with interstitial lung disease (ILDs). METHODS: A total of 1084 subjects including 373 cases of ILDs, 584 cases of non-ILD pulmonary diseases, and 127 healthy individuals were recruited from three clinical centers in China between January 2011 and December 2013. A total of 106 patients undergoing treatments for ILDs in Shanghai Pulmonary Hospital between January 2011 and December 2013 were enrolled. Baseline and posttreatment serum KL-6 levels were determined. RESULTS: Serum KL-6 levels in patients with ILDs were significantly higher than those in patients with non-ILD pulmonary diseases or in healthy individuals (1492.09 ± 2230.08 U/mL vs 258.67 ± 268.73 U/mL or 178.73 ± 71.17 U/mL, all P < 0.05). At the cut-off value of 500 U/mL, the sensitivity and specificity of serum KL-6 as a diagnostic marker for ILDs was 77.75% and 94.51%, respectively. The Kappa value was 0.743 (P < 0.001). The area below the receiver operating characteristic curve was 0.922 with a 95% Confidence interval of 0.904-0.941 (P < 0.001). The posttreatment serum KL-6 levels significantly reduced in patients with improved ILDs, whereas markedly increased in patients with exacerbated ILDs (All P < 0.05). CONCLUSIONS: Serum KL-6 levels might be a promising diagnostic biomarker for ILDs in Chinese patients. The prognostic value of serum KL-6 levels for ILDs remains to be verified by large-scaled studies.

Inter-rater reliability of three most commonly used pressure ulcer risk assessment scales in clinical practice.

The objective of this study was to evaluate inter-rater reliability of Braden Scale, Norton Scale and Waterlow Scale for pressure ulcer risk assessment in clinical practice. The design of the study was cross-sectional. A total of 23 patients at pressure ulcer risk were included in the study, and 6 best registered nurses conducted three subsequent risk assessments for all included patients. They assessed alone and independently from each other. An intra-class correlation coefficient (ICC) was used to determine the inter-rater reliability. For the Braden Scale, the ICC values ranged between 0·603 (95% CI: 0·435-0·770) for the item 'moisture' and a maximum of 0·964 (95% CI: 0·936-0·982) for the item 'activity'; for the Norton Scale, the ICC values ranged between 0·595 (95% CI: 0·426-0·764) for the item 'physical condition' and a maximum of 0·975 (95% CI: 0·955-0·988) for the item 'activity'; and for the Waterlow Scale, the ICC values ranged between 0·592 (95% CI: 0·422-0·762) for the item 'skin type' and a maximum of 0·990 (95% CI: 0·982-0·995) for the item 'activity'. The ICC values of total score for three scales of were 0·955 (95% CI: 0·922-0·978), 0·967 (95% CI: 0·943-0·984), and 0·915 (95% CI: 0·855-0·958) for Braden, Norton, and Waterlow scales, respectively. Although the inter-rater reliability of Braden Scale, Norton Scale and Waterlow Scale total scores were all substantial, the reliability of some items was not so good. The items of 'moisture', 'physical condition' and 'skin type' should be paid more attention. However, some studies are needed to find out high reliable quantitative items to replace these ambiguous items in new designed scales.

Meta-analysis of the adverse effects of long-term azithromycin use in patients with chronic lung diseases.

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment.

BACKGROUND: Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC. METHODS: A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL- 2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≥26.5 pg/ml) and high (>26.5 pg/ml)), IL-2R (low ( = 115 pmol/L) and high (>15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS). RESULTS: Between January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P = 0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P < 0.05). These cytokines remained significant upon multivariate analysis (P < 0.05). CONCLUSION: IL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.

4-Bromo-5-[(2-bromo-ethyl)-sulfanyl]-1,3-dithiole-2-thione.

The title compound, C(5)H(4)Br(2)S(4), consists of a statistically planar, 4-bromo-1,3-dithiole-2-thione unit [maximum deviation from the ring plane 0.001 (2) Å], with a bromo-ethyl-sulfanyl substituent in the 5-position. In the crystal structure, weak inter-molecular S⋯S [3.438 (15) and 3.522 (15) Å] and S⋯Br [3.422 (14) and 3.498 (14) Å] inter-actions generate a three-dimensional supra-molecular architecture.

Effects of different levels of end-expiratory positive pressure on lung recruitment and protection in patients with acute respiratory distress syndrome.

BACKGROUND: It is still controversial as to the implementation of higher positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). This study was conducted to compare the lower and higher PEEP in patients with ARDS ventilated with low tidal volume, to investigate the relationship between the recruited lung volume by higher PEEP and relevant independent variables and to provide a bedside estimate of the percentage of potentially recruitable lung by higher PEEP. METHODS: Twenty-four patients with ARDS were studied. A lung recruiting maneuver was performed, then each patient was ventilated with PEEP of 8 cmH(2)O for 4 hours and subsequently with PEEP of 16 cmH(2)O for 4 hours. At the end of each PEEP level period, gas exchange, hemodynamic data, lung mechanics, stress index "b" of the dynamic pressure-time curve, intrinsic PEEP and recruited volume by PEEP were measured. RESULTS: Fourteen patients were recruiters whose alveolar recruited volumes induced by PEEP 16 cmH(2)O were (425 +/- 65) ml and 10 patients were non-recruiters. Compared with the PEEP 8 cmH(2)O period, after the application of the PEEP 16 cmH(2)O, the PaO(2)/FiO(2) ratio and static lung compliance both remained unchanged in non-recruiters, whereas they increased significantly in recruiters. Changes in PaO(2)/FiO(2) and static lung compliance after PEEP increase were independently associated with the alveolar recruitment. Analyzing the relationship between recruiting maneuver (RM)-induced change in end-expiratory lung volume and the alveolar recruitment induced by PEEP, we found a notable correlation. CONCLUSIONS: The results of this study indicated that the potential for alveolar recruitment might vary among the ARDS population and the higher PEEP levels should be limited to recruiters. Improving in PaO(2)/FiO(2), static lung compliance after PEEP increase and the shape of the pressure-time curve could be helpful for PEEP application.

3-(2-Thioxo-1,3-dithiol-4-ylsulfan-yl)-propane-nitrile.

The title compound, C(6)H(5)NS(4), consists of a planar 2-thioxo-1,3-dithiol-4-ylsulfanyl unit [maximum deviation from the ring plane = 0.0325 (2) Å], with a cyano-ethyl-sulfanyl substituent in the 4-position. In the crystal structure, weak inter-molecular C-H⋯S hydrogen bonds together with S⋯N inter-actions [3.260 (5) Å] form two-dimensional layers in the bc plane.