Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

Oesophageal cancer is one of the most common and lethal malignancies in the world. Despite many efforts, treatment is still ineffective for most cases; thus, the development of preventive strategies is crucial for decreasing the burden presented by this disease. Environmental factors, particularly nitrosamines, are thought to be involved in the genesis of oesophageal tumours, and knowledge about the expression of enzymes capable of activating pre-carcinogens in human oesophagus is very important for the development of preventive measures. We analysed the expression of CYP1A1, CYP1A2, CYP2A6/2A7, CYP2E1 and CYP3A4 mRNA in oesophageal mucosa of 50 patients by semi-quantitative RT-PCR. In five patients, who suffered from squamous cell carcinoma, we measured Nnitrosodimethylamine and N-nitrosodiethylamine metabolism in normal and tumorous tissue. CYP2A6/2A7 mRNA was expressed in 61% and CYP2E1 mRNA in 96% of the patients, but in the latter a lower degree of inter-individual variation was observed. These enzymes were expressed either in the distal or middle portions of the oesophagus of 90% of the patients. CYP1A1, CYP1A2 and CYP3A4 mRNA expression was not detected in any portion of the oesophagus. Oesophageal microsomes activated N-nitrosodimethylamine with a low degree of inter-individual variation and microsomes prepared from the tumour of a patient who strongly expressed CYP2A6/2A7 mRNA activated N-nitrosodiethylamine. We conclude that the human oesophagus expresses CYP2A6/2A7 and CYP2E1 and can activate nitrosamines. Notably, the expression of these enzymes is preferentially localized to the most common sites where tumours arise.

BACKGROUND: The application of CPAP has been used to minimize postoperative pulmonary complications after lung resection surgery. The aim of this study was to quantify both the CPAP effects upon lung function and functional capacity in early postoperative lung resection, as well as to evaluate if CPAP prolongs air leak through the chest drain. METHODS: Thirty patients in the postoperative period of lung resection were allocated into 2 groups: an experimental group, consisting of 15 patients who underwent a 10 cm H 2 O CPAP, and a 15 patient control group, who performed breathing exercises. Arterial blood gas analysis, peak expiratory flow (PEF), respiratory muscle strength, spirometry, and 6-min walk test (6MWT) were assessed in the preoperative period, and repeated postoperatively on the first and on the seventh day (6MWT was repeated only on the seventh day). RESULTS: Significant increases in PEF, muscle strength, and FEV 1 between the first and seventh postoperative day were observed, both in the experimental and in the control group, whereas FVC and P aO 2 increased significantly between the first and seventh postoperative day only in the experimental group. The average loss in 6-min walk distance (6MWD) from preoperative to postoperative day 7 in the experimental group was significantly lower than in control group. When comparing the 2 groups, only 6MWD was statistically different (P < .001). There was no air leakage increase through the drain with the early use of CPAP. CONCLUSION: When compared to breathing exercises, CPAP increases the 6MWD in postoperative lung resection patients, without prolonging air leak through the chest drain.

BackgroundInvasion of the chest wall per se is not a contraindication for tumor resection in non-small cell lung cancer (NSCLC), provided there is no mediastinal lymph node or vital structure involvement. Although widely known to Brazilian surgeons, the ‘resection in bird cage’ technique has never been widely studied in terms of patient survival. Thus, the objective of this study was to evaluate the postoperative consequences and overall survival of extra-musculoperiosteal resection compared with en-bloc resection in NSCLC patients with invasion of the endothoracic fascia.MethodsBetween January 1990 and December 2009, 33 NSCLC patients with invasion of the thoracic wall who underwent pulmonary resection were retrospectively analyzed. Of the 33 patients evaluated, 20 patients underwent en-bloc resection and 13 underwent ‘resection in bird cage.’ For each patient, a retrospective case note review was made.ResultsThe median age at surgery, gender, indication, rate of comorbidities, tumor size and the degree of uptake in the costal margin were similar for both groups. The rate of postoperative complications and the duration of hospitalization did not differ between the groups. Regarding the outcome variables, the disease-free interval, rate of local recurrence, metastasis-free time after surgery, overall mortality rate, mortality rate related to metastatic disease, duration following surgery in which deaths occurred, and overall survival were also similar between groups. The cumulative survival curves between the ‘resection in bird cage’ and en-bloc resection and between stages Ia + Ib and IIb + IIIa + IV were not significantly different (p = 0.68 and p = 0.64, respectively). The cumulative metastasis-free survival curves were not significantly different between the two types of surgery (p = 0.38).ConclusionsIn NSCLC patients with invasion of the endothoracic fascia, ‘resection in bird cage’ is a less aggressive procedure that yields similar results in terms of morbidity and mortality compared with en-bloc resection. Thus, ‘resection in bird cage’ meets the oncologic principles of resection and does not adversely affect the patients in terms of cure.

Background The number of incidental findings of pulmonary nodules using imaging methods to diagnose other thoracic or extrathoracic conditions has increased, suggesting the need for in-depth radiological image analyses to identify nodule type and avoid unnecessary invasive procedures. Objectives The present study evaluated solid indeterminate nodules with a radiological stability suggesting benignity (SINRSBs) through a texture analysis of computed tomography (CT) images. Methods A total of 100 chest CT scans were evaluated, including 50 cases of SINRSBs and 50 cases of malignant nodules. SINRSB CT scans were performed using the same noncontrast enhanced CT protocol and equipment; the malignant nodule data were acquired from several databases. The kurtosis (KUR) and skewness (SKW) values of these tests were determined for the whole volume of each nodule, and the histograms were classified into two basic patterns: peaks or plateaus. Results The mean (MEN) KUR values of the SINRSBs and malignant nodules were 3.37 ± 3.88 and 5.88 ± 5.11, respectively. The receiver operating characteristic (ROC) curve showed that the sensitivity and specificity for distinguishing SINRSBs from malignant nodules were 65% and 66% for KUR values >6, respectively, with an area under the curve (AUC) of 0.709 (p < 0.0001). The MEN SKW values of the SINRSBs and malignant nodules were 1.73 ± 0.94 and 2.07 ± 1.01, respectively. The ROC curve showed that the sensitivity and specificity for distinguishing malignant nodules from SINRSBs were 65% and 66% for SKW values >3.1, respectively, with an AUC of 0.709 (p < 0.0001). An analysis of the peak and plateau histograms revealed sensitivity, specificity, and accuracy values of 84%, 74%, and 79%, respectively. Conclusions KUR, SKW, and histogram shape can help to noninvasively diagnose SINRSBs but should not be used alone or without considering clinical data.