Explore the vast range of titles available.

The microbiota includes different microorganisms consisting of bacteria, fungi, viruses, and protozoa distributed over many human body surfaces including the skin, vagina, gut, and airways, with the highest density found in the intestine. The gut microbiota strongly influences our metabolic, endocrine, and immune systems, as well as both the peripheral and central nervous systems. Recently, a dialogue between the gut and lung microbiota has been discovered, suggesting that changes in one compartment could impact the other compartment, whether in relation to microbial composition or function. Further, this bidirectional axis is evidenced in an, either beneficial or malignant, altered immune response in one compartment following changes in the other compartment. Stimulation of the immune system arises from the microbial cells themselves, but also from their metabolites. It can be either direct or mediated by stimulated immune cells in one site impacting the other site. Additionally, this interaction may lead to immunological boost, assisting the innate immune system in its antitumour response. Thus, this review offers an insight into the composition of these sites, the gut and the lung, their role in shaping the immune system, and, finally, their role in the response to lung cancer.

Background Lungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context. Methods Two hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method. Results The average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months). Conclusions Given our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds. Trial registration NCT02502318.

We investigated the effects of betaine, C-phycocyanin (C-PC), and their combined use on the growth of A549 lung cancer both in vitro and in vivo. When cells were coincubated with betaine and C-PC, an up to 60% decrease in viability was observed which is significant compared to betaine (50%) or C-PC treatment alone (no decrease). Combined treatment reduced the stimulation of NF-κB expression by TNF-α and increased the amount of the proapoptotic p38 MAPK. Interestingly, combined treatment induced a cell cycle arrest in G2/M phase for ~60% of cells. In vivo studies were performed in pathogen-free male nude rats injected with A549 cells in their right flank. Their daily food was supplemented with either betaine, C-PC, both, or neither. Compared to the control group, tumour weights and volumes were significantly reduced in either betaine- or C-PC-treated groups and no additional decrease was obtained with the combined treatment. This data indicates that C-PC and betaine alone may efficiently inhibit tumour growth in rats. The synergistic activity of betaine and C-PC on A549 cells growth observed in vitro remains to be further confirmed in vivo. The reason behind the nature of their interaction is yet to be sought.

This systematic review summarizes the available evidence on respiratory muscle endurance training involving voluntary isocapnic hyperpnoea among patients with chronic diseases. It includes both randomized and non‐randomized controlled trials implementing this exercise training modality performed either alone or in combination with other interventions. It was conducted using the following databases: PubMed, Google Scholar, Physiotherapy Evidence Database (PEDro), Embase, CINAHL, CENTRAL, Cochrane and ReeDOC. It was drafted in accordance with the PRISMA guidelines. The final analysis was conducted on 12 studies ( n  = 257). There was heterogeneity in participants, training modalities and comparators used. The underpowered level of evidence is attributable to the lack of robustness of the original studies, including a lack of description of the intervention, lack of blinding, and missing data. Respiratory muscle endurance training is an exercise training modality that is both safe and feasible, even in the setting of the patient's home. It increases respiratory endurance time. However, its effect on peak oxygen consumption at exercise, maximal work rate, 6‐min walking distance, quality of life, dyspnoea and fatigue remains to be confirmed. In conclusion, this systematic review shows that respiratory muscle endurance training increases respiratory endurance among patients with chronic diseases. The populations that benefit the most and the mechanisms involved remain to be investigated. Further high‐quality studies are needed to understand its role, whether it is performed alone or as an add‐on modality to usual pulmonary rehabilitation programmes. What is the topic of this review? The aim was to summarize evidence on respiratory muscle endurance training involving voluntary isocapnic hyperpnoea among patients with chronic diseases. What advances does it highlight? This systematic review summarizes the available evidence on respiratory muscle endurance training among patients with chronic diseases. It shows that this exercise training modality increases respiratory endurance. The populations that benefit the most and the mechanisms involved remain to be investigated. Further high‐quality studies are needed to understand its role, whether it is performed alone or as an add‐on modality to usual pulmonary rehabilitation programmes.

Background While well-characterised on its molecular base, non-small cell lung cancer (NSCLC) and its interaction with local microbiota remains scarcely explored. Moreover, current studies vary in source of lung microbiota, from bronchoalveolar lavage fluid (BAL) to tissue, introducing potentially differing results. Therefore, the objective of this study was to provide detailed characterisation of the oral and multi-source lung microbiota of direct interest in lung cancer research. Since lung tumours in lower lobes (LL) have been associated with decreased survival, characteristics of the microbiota in upper (UL) and lower tumour lobes have also been examined. Methods Using 16S rRNA gene sequencing technology, we analysed microbiota in saliva, BAL (obtained directly on excised lobe), non-malignant, peritumoural and tumour tissue from 18 NSCLC patients eligible for surgical treatment. Detailed taxonomy, diversity and core members were provided for each microbiota, with analysis of differential abundance on all taxonomical levels (zero-inflated binomial general linear model with Benjamini-Hochberg correction), between samples and lobe locations. Results Diversity and differential abundance analysis showed clear separation of oral and lung microbiota, but more importantly, of BAL and lung tissue microbiota. Phylum Proteobacteria dominated tissue samples, while Firmicutes was more abundant in BAL and saliva (with class Clostridia and Bacilli , respectively). However, all samples showed increased abundance of phylum Firmicutes in LL, with decrease in Proteobacteria . Also, clades Actinobacteria and Flavobacteriia showed inverse abundance between BAL and extratumoural tissues depending on the lobe location. While tumour microbiota seemed the least affected by location, peritumoural tissue showed the highest susceptibility with markedly increased similarity to BAL microbiota in UL. Differences between the three lung tissues were however very limited. Conclusions Our results confirm that BAL harbours unique lung microbiota and emphasise the importance of the sample choice for lung microbiota analysis. Further, limited differences between the tissues indicate that different local tumour-related factors, such as tumour type, stage or associated immunity, might be the ones responsible for microbiota-shaping effect. Finally, the “shift” towards Firmicutes in LL might be a sign of increased pathogenicity, as suggested in similar malignancies, and connected to worse prognosis of the LL tumours. Trial registration ClinicalTrials.gov ID: NCT03068663 . Registered February 27, 2017.

Abstract Objectives The increasing use of CT imaging and the implementation of lung cancer screening have led to a rising detection of pulmonary nodules. Accurate management requires reliable localization techniques enabling pathological diagnosis and potential curative resection. This study compared hook-wire localization and cone-beam computed tomography (CBCT)-guided detection in terms of diagnostic yield. Methods A retrospective analysis was performed in 2 French academic centres, including 260 patients with 266 nodules (January 2012-May 2019). The primary end-point was diagnostic yield, defined as the proportion of successfully localized nodules. Secondary end-points included localization and operative times, peri- and postoperative complications, chest tube duration, and hospital stay. Results Diagnostic yield was 88.0% with hook-wire localization and 96.9% with CBCT, corresponding to an absolute difference of 8.9% (95% CI, –0.2 to 17.9; P = .053). Complication rates (P = .63), drainage duration (P = .13), and hospital stay (P = .16) did not differ between groups. Operative time (P = .042) and localization time (P = .001) were significantly longer with CBCT and hook-wire, respectively. Conclusions Hook-wire and CBCT localization demonstrated comparable diagnostic yields and acceptable safety profiles. CBCT required longer operative room utilization, whereas hook-wire placement was performed in the radiology department, saving resources for other surgeries. The widespread use of CT imaging in clinical practice, together with advances in image resolution and the implementation of lung cancer screening programs in smokers, has led to a steady increase in the detection of pulmonary nodules. Graphical abstract

Background Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome , and is associated with an increased risk of death. Studies conducted on animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients. Methods Muscle biopsies were performed during scheduled interventions in early-stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients (n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real-time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered. Results We found an increased expression of several UPS and autophagy-related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P < 0.01), MAFbx (+68 to 84%, P = 0.02), Hdm2 (+37 to 59%, P = 0.02), and MUSA1/Fbxo30 (+47 to 106%, P = 0.01) and the autophagy-related genes CTPL (+33 to 47%, P = 0.03) and SQSTM1 (+47 to 137%, P < 0.01) were overexpressed. Mass spectrometry identified >1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxifica-tion, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co-expression network analysis. Conclusions We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early-stage LC vs. long-term renal failure). This strongly suggests that a common atrophying programme exists independently of the disease in human.

IntroductionIn the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact.Methods and analysisThe French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients.Ethics and disseminationThe protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals.Trial registration numberNCT02502318.

IntroductionSurgery is the standard curative treatment for lung cancer but is only possible in patients with local tumour and preserved exercise capacity. Improving fitness before surgery can reduce postoperative complications and mortality. However, preoperative rehabilitation remains difficult to implement for several reasons. We aim to investigate the effectiveness of an intensive 3-week home-based preoperative exercise training programme on hospital discharge ability, postoperative complications and physical performance in patients with chronic obstructive pulmonary disease (COPD) who are eligible for lung cancer surgery.Methods and analysisWe designed a multicentre randomised controlled trial. The randomisation sequence will be generated and managed electronically by a research manager independent of assessments or interventions. We will recruit 90 patients with COPD and a diagnosis of lung cancer from four university hospitals. The rehabilitation group (R group) will receive a standardised preoperative home exercise programme for 3 weeks, combining both high-intensity training and usual physical therapy. The R group will perform 15 training sessions over 3 weeks on a cycloergometer. A physical therapist experienced in pulmonary rehabilitation will visit the patient at home and supervise one session a week. The R group will be compared with a control group receiving preoperative usual physical therapy only. The primary outcome will be hospital discharge ability assessed with a 10-item list. Secondary outcomes will be postoperative course (complication rate and mortality) as well as pulmonary function, exercise capacity and quality of life assessed 1 month before and the day before surgery.Ethics and disseminationThis protocol has been approved by the French health authority for research (2016-A00622-49) and the research ethics committee/institutional review board (AU1267). Adverse events that occur during the protocol will be reported to the principal investigator. The results will be published in an international peer-reviewed journal.Trial registration numberNCT03020251.

Purpose Preclinical data pointed to 99m Tc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify 99m Tc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone 99m Tc-hydroxymethylene diphosphonate (HMDP) radiotracer. Methods Three osteoarthritic human tibial plateaux and four tibiofemoral joints were incubated with 99m Tc-NTP 15-5 and 99m Tc-HMDP for 2 h. Affinity of tracers for cartilage was determined by visual analysis of SPECT/CT acquisitions and measurement of cartilage to cortical bone uptake ratios. Results Cartilage to cortical bone uptake ratios were 3.90 ± 2.35 and 0.76 ± 0.24, respectively, for 99m Tc-NTP 15-5 and 99m Tc-HMDP radiotracers. Visual analysis of fused SPECT/CT slices showed selective, intense 99m Tc-NTP 15-5 accumulation in articular cartilage, whereas 99m Tc-HMDP binding was low. Interestingly, a cartilage defect visualized on CT was clearly associated with focal decreased uptake of 99m Tc-NTP 15-5. Conclusion The tracer 99m Tc-NTP 15-5 is of major interest for human cartilage molecular imaging and could find clinical applications in osteoarthritis staging and monitoring.